Domenico Orsini d'Aragona (Naples, 5 June 1719 – Rome, 10 January 1789) was an Italian, Roman Catholic Cardinal.
He was born to Ferdinando Bernualdo Filippo Orsini, the 14th Duke of Gravina, and his second wife, Giacinta Marescotti-Ruspoli.
Also that year, he was named by King Charles VII of Naples to be ambassador to the Vatican.
Widowed in 1742, Pope Benedict XIV nominated him a cardinal deacon, since he had never taken priestly orders.
Domenico was entailed with forwarding the suppression of Jesuits, and tried to advance the beatification of the former antagonist of the order, Juan de Palafox y Mendoza.