Born at Naples and son of a patriot, he was put several times in prison by the Bourbons, the King of Naples, because a sustainer of Italian Unity. In 1962, when Naples was attached to the new united Italian kingdom, he was freed and became university teacher of Italian literature. In 1873 he was created Senator.

Settembrini homosexuality was first mentioned in 1977, when his short novel I neoplatonici (The Neoplatonics) was first published. The work is a homoerotic fantasy set in ancient Greece which Settembrini wrote while in prison. The work tells the story of two youths in love with each other, who become lovers; it includes descriptions of anal intercourse between the two men.

The absolutely positive and serene image it presents of homosexuality is noteworthy. Settembrini presents homosexual love as a form of human beahaviour capable of giving joy and satisfaction. He also portrays it as a relationship with both emotional and erotic dimensions, a relatively rare approach in 19th century writing.