Despotović () is a Serbian surname, derived from word despot ("master, lord"). Notable people with the surname include:
Đorđe Despotović (born 1992), Serbian footballer Frane Despotović (born 1982), Croatian futsal player Jelena Despotović (born 1994), Montenegrin handball player Jovan Despotović (born 1952), Serbian art historian and critic Petar Despotović (born 1988), Serbian basketball player Ranko Despotović (born 1983), Serbian footballer Veljko Despotović (1931–2013), Serbian film and television production designer Vesna Despotović (born 1961), Serbian basketball player Zoran Despotović (born 1965), Serbian politician