After the conquest of Constantinople by the Franks in 1204 and the dismemberment of the Byzantine Empire to the Franks and Venetians, decentralized Byzantine provinces in Nice and Epirus were created. Michael I Komnenos Doukas (1205-1215), cousin of the Byzantine emperors Isaac II and Alexios II Angelos, founded the so-called "Domain of Epirus" with its capital at Arta. In Giannina he settled, around 1210, many Byzantine families from Constantinople (Philanthropini - Stratigopoulos - Melissenoi etc.). Michael I, was characterized by the metropolitan of Nafpaktos, Ioannis Apokafkos, as the "tektinamenos", ie the one who built it, "the Ioannina polidion and in education of the castle is erected." Since there was an earlier fortification he probably means that wider enclosure was constructed to also contain the outer of the old wall houses and possibly the fortification of the peninsula neck. In the enlarged Castle, Michael I, settled refugees from Constantinople and other Latin-occupied areas. Later his brother Theodore (1215-1230) legalized them again, probably to appease protests by indigenous residents against the refugees.
From the start, belligerent competition for claiming the restoration of the empire among the states of Epirus and Nice was developed. In 1259 the battle of Pelagonia was decisive, during which Michael II (1231-1267 / 8) of Epirus was defeated by the army of Nice. Then, Arta was occupied and Ioannina was besieged unsuccessfully. In 1261 Constantinople was conquered by the army of Nice. The state of Epirus retained its autonomous character and its relationship with the liberated Constantinople went through different phases and sometimes rivalry.
After the death of Michael II, the territory was partitioned among his sons. Epirus came under Nikephoros I (1267-1296). His marriage to Anna Palaiologina, niece of the Byzantine emperor Michael VIII, is attached to a kind of trusteeship of Constantinople, which soon turned because of the controversy about the union of the church (1276-1277). In a sense, Ioannina probably joined the Byzantine Empire around 1284, to ensure autonomy, but soon approached Arta again. In 1290 or 1292 the army of the Byzantine Emperor besieged unsuccessfully the fortified city of Ioannina.
Expiring the13th century, the city of Ioannina is an important center of the region with a strong wall, temples and mansions. At that time the island becomes an important monastic center. The well-known Byzantine families Filanthropinos and Stratigopoulos establish monasteries dedicated to Saint Nicholas. The importance of the city is evident by the fact that when, in 1304, Charles II of Naples d' Anjou campaigned against Arta, Anna fled to Ioannina, where according to historical sources of the time describe its castle as an impregnable castle.
The last Komninodoukas archbishop Thomas, son of Nikiphoros was murdered in 1318 by his nephew Nicholas Orsini, Count of Cephalonia. The residents of Ioannina refused to acknowledge the new ruler, so the city asked her affiliation to the Byzantine emperor. Syrgiannis Paleologos, commander of the western Byzantine possessions, received the city of Ioannina. In return the bishopric of the city was promoted to Cathedral (1318) and kept the property, while the residents were granted many privileges. Two imperial decrees of the years 1319 and 1321 by the Emperor Andronicus II Palaeologos ensured the non- concession of Ioannina and the surrounding castles to the Franks and also included tax benefits and exemptions for residents of the city.
"Kastrinoi Ioanniniotai", except those who belonged to military forces, were not obliged to offer military services outside their city. However, the governor of the city was appointed by the emperor. At that time Ioannina lived in great prosperity, "the city on the continent ... memestotai oikitoron, flourishes in wealth ..." as in the first imperial decree. According to the historian L.Vranousi in these texts a kind of early bourgeois society with nobility is described, a society which knows how to govern themselves in proportion with the flourishing states of the cities of Italy.
Nicholas Orsini married the wife of Thomas, Anna and received the title of the bishop of Constantinople with the commitment not to attack Ioannina. But he, taking advantage of the civil war between Andronikos B and C, which has in the meantime erupted between the Byzantine capital, besieged the city unsuccessfully. In 1323 during the armed conflict with his brother John, Nicholas was killed. John persuaded Ioannina to accept him, winning their sympathy with renewal of privileges (1330). In 1337 or earlier he was murdered by his Byzantine wife and residents of Ioannina swore faith to her and her son Nikiforos. Meanwhile, in 1338, the emperor Andronicus III came to the Epirus in order to strengthen the Byzantine domination and especially to confront the Albanian incursions.
During the civil war between John V Palaiologos and John VI Kantakouzinos (1341-7), when the latter became ruler of Epirus and Thessaly, allowed the Serbs to be imposed. Ioannina probably had already been occupied since 1346, while the conquest of Epirus and Thessaly was completed in 1348 and was assigned to the half-brother of Stephen Dushan, Simeon Uresis. In 1366 the people of Ioannina asked Symeon to indicate their ruler in order to provide protection from the attacks of the Albanians. He sent them his groom, Thomas Prelioumpovits (1367-1384).
His acceptance by the city's residents was not unanimous. Thomas took harsh measures for the rulers and the local church, expelled the bishop and took away ecclesiastical estates. He imposed taxes and military burdens which however were necessary to confront the pressing attacks of the Albanians, who had prevailed in Arta and Aitolokarnania. In the decade of 1370 Ioannina was repeatedly besieged by Albanians and the area was deserted. In his wars, Thomas collaborated with the Turks leading Turkish facilities in Epirus. In 1382 he requested and received the title of archbishop by the Emperor Manuel II, while two years later he was assassinated by his bodyguard. The marble tomb was found in 1795 in the bedrock of Ali Pasha's palace.
Thomas made extensive interventions in the walls. As it is mentioned in historical sources of the period "to his custody he built castles with towers shapely and built palaces big and shapely." Probably the strengthening of the fortification was to confront the Albanians perhaps before the attack in 1379. It is his work, the construction of the fortress tower right of the main entrance of the castle, as well as the gate of the northeastern citadel, which served to strengthen the residence of the archbishop. Many and quite generous were the tributes of Thomas to Monasteries (Great Meteor, Great Lavra, Gavaliotissa Vodena). After his assassination, Ioannina was ruled by the Franks with the consent of the Lords. The widow of Thomas, Maria Angelina Doukaina Palaiologina married Prince Izaou Bouantelmonti of the house Atzagioloi in Florence, Lord of Cephalonia. Izaou was named in 1386 Archbishop by the Byzantine emperor and returned the property of the church. At that time the raids of Albanians continued on the outskirts of Ioannina, with the result in 1388-9 by Izaou to declare subordination to the Sultan to face the Albanian threat. That fact in some of the historical sources is regarded as the first Turkish conquest of Ioannina.
Izaou died in 1411 and was succeeded, at the invitation of the local aristocracy, by Charles A. Tocco, duke of Cephalonia, who like his predecessors, took in 1415 the title of Archbishop by the Byzantine emperor. In 1416 Charles captured Arta and ruled until 1429. The "Chronicle of the Toccos," written in 1429 is an epic in verse, which refers to the heroic deeds of Charles and his brother Leonardo. The nephew of Charles I, Charles II and illegitimate sons, hardly had time to rule, as in 1430 the city succumbed to the Turks.
According to most researchers, the Byzantine character of the city remained at the time of the Serbian and the Italian princes, as they undertook their duties after negotiations with the local aristocracy and received the title of archbishop by the Byzantine emperor. Also, the city has known the Albanian occupation, as the Chronicle of Ioannina mentions: "..only the city of Ioannina not surrendering to the territory of the Albanians." The Kastrinoi aristocracy owns villages and land. Crafts and trade is developed. The Chronicles of Ioannina and the Tocchi, written in the early 15th century give important information on the history, topography and social stratification of the city. The Castle has a great reputation at that time and is characterized in the sources: "brilliant, royal and noble."
According to a manuscript of 1819, a copy of the 'Kouvaras ", a chronography of the 14th to 15th century, there were five monasteries in the city and twentyfive churches, of which eighteen were in the castle. It is reported that in the place of Ali Pasha's palace there was a temple complex of the Pantocrator, while in the edge of the palace, the saved the church of Metropolis 1779, is mentioned, perhaps in the place of Fethiye. So, in the late Byzantine period the southeast acropolis, the old citadel of Voimoundos, was occupied by religious institutions perhaps Bishopric and houses towards the part of today's city.
There is ambiguity as to the housing situation outside the castle. Many scholars believe that during the medieval period (perhaps since the 12th century) there were neighborhoods outside the wall. In another aspect, the large area enclosed within the walls, was sufficient for the population of the city and so outside the walls there were only rudimentary commercial facilities, according to the medieval custom of a flea market at the gates of cities, practice, established in the city under Turkish rule. Moreover, in late Byzantine sources there is no reference to burco, ie settlement outside the village walls or a trade-Boris, but only vineyards are listed. From the monasteries out of the walls the Archimandreiou, Agia Paraskevi, Agios Athanasios etc. are mentioned.