The authors agree that this surname derives from the personal name Isidoros, of Greek origin, meaning "gift of Isis", the goddess of motherhood and fertility in Egyptian mythology, venerated also in the ancient Greco-Roman world. The name passed into Late Latin as Isidorus and was then Italianized as Isidoro. Its transformation into a surname comes from the personal names of the founding ancestors of each family.

A. Bongioanni notes that the name was borne by twelve saints, of whom the most venerated in Italy are Saint Isidore of Alexandria (died 404, celebrated on 15 January), Saint Isidore of Seville, a Father of the Church of the 6th century (celebrated on 4 April), Saint Isidore of Madrid (died 1170, patron of farmers, celebrated on 10 May), and, in Venice, Saint Isidore of Chios, whose body is preserved in the basilica of San Marco (celebrated on 14 May). Bongioanni adds that in surnames this form converges with Teodoro.

E. Rossoni specifies that the Late Latin name Isidorus was borne, among others, by Sanctus Isidorus Hispalensis (approximately 560–636). As for geographical distribution, the forms Isidor and Isidoris are almost unique, while Isidori is typical of the central strip comprising the Marche, Umbria and Lazio. The form Isidoro shows specific areas in the province of Pescara, in Sant'Antimo in the Naples area, and in the province of Brindisi.