D'Onofrio (sometimes spelled Donofrio) is a surname of Italian origin. People bearing this name include the following:
- Beverly Donofrio (born 1950), American author
- Brian D'Onofrio, American psychologist
- Carol D'Onofrio (1936–2020), American public health researcher
- Denis D'Onofrio (born 1989), Italian footballer
- Dominique D'Onofrio (1953–2016), Italo-Belgian football coach
- Elizabeth D'Onofrio (born 1957), American film producer, actress, and acting coach; sister of Vincent D'Onofrio
- Katerina D'Onofrio (born 1978), Peruvian actress
- Mark D'Onofrio (born 1969), American former college football coach and former professional player
- Nicola D'Onofrio (1943–1984), Italian Camillian monk
- Vincent D'Onofrio (born 1959), American actor; brother of Elizabeth D'Onofrio