The authors differ both on the geographical origin and on the etymology of this surname. E. Rossoni notes that it shows areas of concentration in the Marche —especially in the Ascoli Piceno area—, in the Chieti area, at Francavilla al Mare, and in Rome and Civitavecchia. According to Rossoni, it could derive from an archaic form of the demonym of Matrice, in the province of Campobasso, indicating the geographical origin of the founder of the line; he also proposes a derivation from the term matricaria —chamomile—, which would allude to an activity in herbalism or paramedical care practised by the founder of the line.

V. Blunda, by contrast, considers it a Sicilian surname of Germanic root, derived from the compound mathal gardi, formed by mathal ("assembly, place of legal gathering") and gardi ("enclosure, precinct"), with the overall sense of "precinct of the assembly" or "enclosure of the council". Blunda links it as a phonetic variant of Mandrigardo, with the preservation of the intermediate consonant proper to some adaptations of central and southern Italian. He expressly rules out the connection with matricario or with Matrice as a popular etymology without foundation, noting that the formal resemblance is the product of phonetic chance.