The surname Mattei derives from the given names Matteo and Mattia, both rooted in the Christian tradition. E. De Felice and F. De Laurentiis agree that both names share the same etymology: the Hebrew theophoric name Mattityà, formed from mattat ("gift") and Yà, an abbreviation of Yahweh ("God of Israel"), yielding the meaning "gift of God." The two names differ in their transmission: Matteo reached Italian through the Greek Matthaios and the Latin Mattheu(m), while Mattia reflects a separate adaptation into Greek, Maththias, and into Latin, Mat(t)hia(m). This same etymology is confirmed by a third source, which records the surname as deriving from the given name Matteo, itself traced to the Hebrew Mattityà.

De Felice adds that these names refer, respectively, to Saint Matthew — apostle, evangelist, and martyr in Ethiopia — and to Saint Matthias, the apostle chosen to replace Judas. He further notes that the names spread with particular intensity in regions marked by Greco-Byzantine influence, where the Greek aspirate -th- was rendered as f, s, or z, giving rise to the variant forms Maffeo, Masseo, and Mazzeo. The corresponding surname variants show a clear regional distribution: Maffei predominates in the Veneto and Lombardy; Massei is more characteristic of central and southern Italy; Mazzei is most frequent in the south.

De Felice also records that the Latinized form Matteis belongs specifically to the area of Bergamo, where documentary evidence already attests to families bearing this surname at the end of the fourteenth century and the beginning of the fifteenth.