Born ca. 1297, Demetrios was the youngest of Andronikos II's sons. In ca. 1304, he was sent to the court of the Serbian ruler Stephen Uroš II Milutin, intended to become his successor; his stay there was short, however, and he soon returned to Constantinople. In 1306 he was named to the highest court rank, that of Despot. In the Byzantine civil war of 1321–1328, Demetrios sided with his father against his nephew, Andronikos III Palaiologos. In 1327–1328, during the last stage of the civil war, he served as governor of Thessalonica. Eventually he was forced to flee to Serbia, while Andronikos III managed to take his wife and children captive, but Demetrios returned to Constantinople after Andronikos III's final victory. Demetrios was accused of conspiring against his nephew in 1336/37, but Andronikos III dropped the charges. Nothing more is known of him after 1343.