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Niccolò Gaddi was born in Florence in 1499, the son of Taddeo Gaddi and Antonia Altoviti. He was a direct descendant of medieval painter Taddeo Gaddi. He was the uncle of Cardinal Taddeo Gaddi and a relative of Catherine de' Medici.
He was the administrator of the metropolitan see of Cosenza from January 31, 1528 until June 21, 1535. In 1533, he was named cardinal protector of the Kingdom of France. He was administrator of the see of Sarlat from December 12, 1533 until July 3, 1545.
He participated in the papal conclave of 1534 that elected Pope Paul III. On January 9, 1545, he opted for the deaconry of Santi Vito, Modesto e Crescenzia. He participated in the papal conclave of 1549-50 that elected Pope Julius III. On February 28, 1550, he opted for the deaconry of Santa Maria in Domnica and on June 27, 1550 for the deaconry of Santa Maria in Via Lata. At this time, he became cardinal protodeacon. On November 20, 1551, he opted for the order of cardinal priests and his deaconry was raised pro illa vice to titulus.
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