He married Giulia Matuzzi, daughter of Pietro Matuzzi and Isabella, an illegitimate daughter of Pope Alexander VI[1] and they had two sons, Giovanni Batista Mattei and Alessandro Mattei.
[2] He became Conservatore di Roma and in 1582 he began construction on the Villa Celimontana in Rome.
[citation needed] Mattei was a close friend and patron of Michelangelo Merisi da Caravaggio and commissioned a number of works including the Supper at Emmaus, John the Baptist (Youth with a Ram) and The Taking of Christ (for which Mattei and his brother paid 125 scudi[3]).
He added an entail though, stating that no part of the furniture or furnishings considered to be a part of the Villa Mattei should be removed so as to ensure the villa would remain as it had been while he was alive.
However, future generations had the entail broken (by Pope Benedict XIV) and the villa's contents were eventually divided and sold.