He was the son of Agostino Ansano Polidori (1714–1778), a physician and poet who lived and practised in his native Bientina, near Pisa, Tuscany.

On 29 January 1793,[3] Gaetano Polidori married an English governess, Anna Maria Pierce of Middlesex (b. c. 1774[4]), and they had four children.

His oldest son John William Polidori was a physician to Lord Byron and author of the first vampire story in English, The Vampyre (1819).

After Gabriele's death in 1854, Frances quickly burned the remaining copies of his book Il Mistero dell' Amor Platonico del Medio Evo.

Frances sat for Gabriel for some of his early paintings, for example, The Girlhood of Mary Virgin, in which she modelled for Saint Anne.