He was educated at the Jesuit College, in Orvieto where he received a doctorate in utroque iuris, both civil and canon law.

[2] He was elected titular archbishop of Berito in 1833 and was consecrated by Cardinal Bartolomeo Pacca.

Sermattei was elevated to cardinal and appointed cardinal-priest of San Giorlamo degli Schiavoni in 1836.

He participated in the Papal Conclave of 1846 which elected Pope Pius IX and was the head of the group of three cardinals that governed Rome during the pope's absence in Gaeta between 1849 and 1850, known as the Red Triumvirate.

He also held the following titles: Sermattei died on 10 February 1861 in Rome.