Pope Alexander VI(Played by John Doman)
First Duke of Gandia
Juan, Cesare, Lucrezia, and Goffredo are Rodrigo's children by Vannozza—and officially the children of her and Rodrigo's late cousin, Domenico Giannozzi d'Arignano.
Giovanni "Juan" Borgia
Second Duke of Gandianote(Played by Stanley Weber)
Rodrigo and Vannozza's eldest son, brother to Cesare and Lucrezia, married to Maria Enriquez de Luna, father of Isabel and Juan.
- Asshole Victim: Rodrigo is the only one who's sad when he dies. Even his own mother said he kinda deserved it.
- Big Brother Bully: To Juan and Lucrezia.
- Parental Favoritism: He's Rodrigo's favorite
- The Un-Favourite:
but not his mother's. Juan laments that she let him be sent away to Spain when he was 12.Vannozza: Thank God I have another son. Thank God I have Cesare.
Duke of Valentinois(Played by Mark Ryder)
- Large Ham
- Magnificent Bastard: Cesare grows to be one over the course of the series, going from a self doubting priest in training to the most feared man in Italy.
- Emotional Bruiser: Cesare is as brutal and as emotional as they come.
- Mr. Fanservice: Cesare has no problem walking around shirtless or naked.
- We Used to Be Friends: Him and Alessandro were friends when they were classmates in Pisa.
- Morality Pet: His sister, his children, his wife when he remembers her, his mother sometimes
- In-Series Nickname: "il Valentino"
- The Un-Favourite: Rodrigo does love him, but Juan is the favorite
- Parental Favoritism: though Cesare is Vannozza's favorite.