He learned Greek and Hebrew towards the latter part of his life, and was appointed in 1518 prefect of the Vatican Library.
Acciaioli worked mainly on translating Ancient Greek texts, including Olympiodorus on Ecclesiastes, a treatise of Eusebius against Hierocles, and Theodoret's Cure of the false Opinions of the Gentiles, and some other pieces.
In addition to his translations, Acciaiuoli also wrote a panegyric on the city of Naples; a Liber de vindicta Dei contra peccatores; and poems.
Acciaiuoli's own copy of his translation of Eusebius is in the Vatican Library.
It includes corrections and annotations by him, and is signed on the title page, "F. Zenobii Acciolj".