The House of Kantakouzenos (Greek: Καντακουζηνός), latinized as Cantacuzenus and anglicized as Cantacuzene, was one of the most prominent noble families of the Byzantine Empire in the last centuries of its existence. The family was one of the Empire's wealthiest and provided several prominent governors and generals, as well as two Byzantine emperors. The Kantakouzenoi intermarried extensively with other Byzantine and Bulgarian noble families such as the Palaiologoi, the Philanthropenoi, the Asen, and the Tarchaneiotes. The feminine form of the name is Kantakouzene (Greek: Καντακουζηνή), latinized as Cantacuzena.
The family's surname derives from the locality of Kouzenas near Smyrna. They first appear in the reign of Alexios I Komnenos, when a member of the family campaigned against the Cumans. In the Komnenian period, members of the family are attested as military officials: the sebastos John Kantakouzenos was killed in the Battle of Myriokephalon, while his probable grandson, the caesar John Kantakouzenos, married Irene Angelina, the sister of Isaac II Angelos. By the time of the Fourth Crusade, the Kantakouzenoi were among the greatest landholders in the Empire.
They remained prominent in the Palaiologan period. Michael Kantakouzenos was appointed governor of the Morea in 1308 and his son, John VI Kantakouzenos, rose to be megas domestikos, regent, and eventually emperor (1341–1354) before resigning and retiring to a monastery after a failed civil war. John VI's eldest son Matthew also reigned as his co-emperor and as a pretender (1353–1357) before being captured and forced to resign as well. John's younger son Manuel Kantakouzenos remained despotes of the Morea from 1349 until 1380. Of John VI's daughters, Helena Kantakouzene married John and Matthew's rival John V Palaiologos (r. 1341–1391), Maria married Nikephoros II Orsini of Epirus, and Theodora married the Ottoman bey Orhan I.
Matthew's two sons, John and Demetrios, ruled briefly the Morea. John died childless. The possible descendants of Demetrios (the exact parentage is uncertain) were Georgios, called "Sachatai"; Andronikos, the last megas domestikos of the Byzantine Empire; Eirene, who married Đurađ Branković; Thomas, who served in Branković's court; Helena, who became the second wife of David of Trebizond; and an unnamed daughter, who may have become queen of Georgia.