He studied at the seminary in Savona before entering the Congregation of the Clerics Poor Regular of the Mother of God of the Pious Schools, more commonly known as the Piarists, on 23 October 1870, in Liguria.

Mistrangelo was ordained to the priesthood on 17 March 1877, and then taught at the Piarist schools of Finalborgo, Carcare, and Ovada.

He received his episcopal consecration on the following 11 May from Cardinal Lucido Parocchi, with Archbishop Antonio Grasselli OFM Conv, and Bishop Luigi Canestrari serving as co-consecrators, in the Church of San Pantaleone.

Pope Benedict XV created him cardinal-priest of S. Maria degli Angeli in the consistory of 6 December 1915.

Cardinal Mistrangelo died from gastric poisoning[1] in Florence, at the age of 78; his tenure as archbishop lasted for thirty-one years.