Giacomo Simonetta (1475–1539) was an Italian Roman Catholic bishop and cardinal.

Giacomo was born in Milan, the son of Giovanni and his second wife Catarina Barbavara, daughter of Marcolino Barbavara.^[1]

He studied law in Milan.^[1] In 1494, he became a member of the Collegio degli Avvocat in Milan.^[1] He became a consistorial advocate in 1505.^[1] He became an auditor of the Roman Rota in 1511 and served as the dean of the Roman Rota from 1522 to 1528.^[1] He also participated in the Fifth Council of the Lateran from 1512 to 1517.^[1]

On 17 July 1528 he was elected bishop of Pesaro.^[1] He was consecrated as a bishop on 14 September 1529 in the chapel of San Lorenzo in Piscibus by Cardinal Agostino Spinola.^[1] While Paolo Capizzuchi was absent from Rome, Pope Clement VII name Bishop Simonetta to replace him in the matter of the divorce of Henry VIII of England.^[1]

Pope Paul III created him a cardinal priest in the consistory of 21 May 1535.^[1] He received the red hat and the titular church of San Ciriaco alle Terme Diocleziane on 31 May 1535.^[1]

On 20 December 1535 he was named bishop of Perugia.^[1] He and six other cardinals were named on 8 April 1536 to a congregation for celebrating an ecumenical council.^[1] He was named bishop of Lodi on 4 August 1536, though he later resigned the government of the diocese in favor of his nephew Giovanni Simonetta on 20 June 1537.^[1] He opted for the titular church of Sant'Apollinare alle Terme Neroniane-Alessandrine on 28 November 1537.^[1] On 10 December 1537 he resigned the administration of Pesaro in favor of his nephew Ludovico Simoneta, who later became a cardinal himself.^[1]

A short time later, he became prefect of the Apostolic Signatura.^[1] On 7 January 1538 he and eight other cardinals were named to a second congregation charged with preparing for an ecumenical council.^[1] On 6 February 1538 he was appointed to the diocese of Nepi-Sutri.^[1] He resigned the government of Perugia on 20 July 1538.^[1]

He mediated a dispute between the Republic of Florence and the Republic of Siena for control over Montepulciano and was able to broker a mutually agreeable solution.^[1] In 1539, he was the papal legate to the Council of Vincenza, along with Cardinals Girolamo Alexander de Motta and Bonifacio Ferrero.^[1] On 10 January 1539 he became Camerlengo of the Sacred College of Cardinals.^[1]

He died in Rome on 1 November 1539.^[1] He is buried in Trinità dei Monti.^[1]