It is a very rare patronymic surname, formed by the particle D' —an elided form of di, "son of"— followed by the medieval personal name Amaddio. The nominal base refers to the Latin forms Amo Deus or Ama Deus, with the sense of "may he love God" or "loved by God", a Christian devotional name frequent in medieval onomastics. This origin gave rise to a wide family of surnames that includes Amaddeo, Amadei, Amadeo, Amadio, Amedei, Amedeo, Amodeo and Amodio.

E. Rossoni notes that D'Amaddio seems typical of the Pistoia area, in Tuscany, and that in some cases it could have been attributed to abandoned children. The nearby variants D'Amadio and D'Amodio present different distributions: the first is documented in Sante Marie, in the L'Aquila area, and in Rome; the second is specific to Sant'Antimo and Melito di Napoli, in the Naples area.

R. Sgaramella records the form Amaddio —without the particle— in Aversa, in the province of Caserta (Campania), from 1783, with the document Francesco Amaddio. V. Blunda, in his catalogue of Sicilian surnames, glosses this form as che sia amato da Dio ("may he be loved by God"), confirming its character as a Christian augural name. Rossoni also documents Amaddio in Rosolini, in the province of Syracuse, and in Catania, which places this variant as typically Sicilian.