According to E. De Felice, the surname —widespread though not very frequent in Tuscany and the Neapolitan area— derives from a nickname formed from an occupational name, acciàio or acciaiòlo, documented in Latinised form (Acciai(u)olus) as early as the 12th and 13th centuries. This term designated someone who produced or traded acce, that is, raw threads of hemp, flax or cotton, used in various manufactures. In some cases, especially in the south, it could also be related to acciàio ("steel") or to àccia, an old variant of azza, a bladed weapon of war, which would broaden its interpretation towards metallurgical or military spheres.

For his part, E. Rossoni proposes an interpretation centred on the trade, linking the surname to nicknames related to the work of the blacksmith, or to the medieval term accia ("axe, blade"), derived from the Germanic hacke. He also notes the early presence of the surname in Italian history: as early as the 13th century the Acciaioli lineage is documented in Florence, which came to hold titles such as Dukes of Athens and Counts of Melfi. He also highlights the figure of the Tuscan humanist Donato Acciaioli, active in the 15th century, which confirms the historical relevance of the surname.