The Gattilusi (singular Gattilusio) were a powerful Genoese family who controlled a number of possessions in the northern Aegean from 1355 until the mid 15th century.

Francesco Gattilusio gained the favor of Byzantine Emperor John V Palaiologos by helping him oust a rival to the throne, John VI Kantakouzenos, in 1354. As reward, Gattilusio was given lordship of the island of Lesbos (and its stronghold, Mytilene) from July 1355, as well as the hand in marriage of the emperor's sister, Maria. The Gattilusi possessions grew to include, among others, the islands of Imbros, Samothrace, Lemnos and Thasos, and the land city of Aenos (modern Enez in Turkey). From this position, they were heavily involved in the mining and marketing of alum, useful in textile production and a profitable trade controlled by the Genoese.

After the Fall of Constantinople in 1453, the Gattilusi briefly retained control of their possessions under Ottoman suzerainty, but were forced out within a few years. In 1456, the Ottomans appointed a native Greek historian, Michael Critobulus, as governor of Imbros, and likewise removed the Gattilusi from power in the remainder of their possessions, with the exception of Lesbos, which they were permitted to retain in return for an annual payment of 4,000 gold pieces. The lord of Lesbos, Domenico Gattilusio, was murdered and briefly succeeded by his brother Niccolò, before an Ottoman fleet captured the island in September 1462, sending Niccolò as prisoner to Constantinople (where he was later executed) and putting an end to the family's power.