Giandomenico Spinola (1580 – 11 August 1646) (also Giovanni Domenico Spinola) was an Italian cardinal of the Roman Catholic Church.
Spinola was born in 1580 in Genoa. Though few records exist detailing his family background or education, he is listed as Questore (commissioner) of the Pontifical Office of the Treasury in his home town during the reign of Pope Paul V.
Later Spinola moved to Rome where, under the guidance of Archbishop of Genoa, Antonmaria Sauli, he was appointed to a number of administrative church positions.
Spinola was sent to the Archdiocese of Messina to act as administrator in 1625 and upon his return to Rome in 1626 he was elevated to the office of cardinal, with the Basilica of San Clemente as his titular church. He was also named as Protector of his homeland, the Republic of Genoa, becoming its official representative to the Holy See.
In 1629 Spinola was also given the title of Cardinal Priest of the Church of Santa Cecilia in Trastevere, holding both until he gave up that of San Clemente on 17 August 1637. In November 1630 he was named the Archbishop of Acerenza and Matera. He was transferred to the episcopal see of Luni-Sarzana on 26 April 1632, retaining the personal rank of archbishop. He was again transferred, this time to the Diocese of Mazara del Vallo in Sicily as of 1 December 1636, still retaining the rank of archbishop.