The authors agree that this surname comes from the Greek given name Alèxios, meaning "defender" or "protector", formed on the verb aléxein ("to defend").

A. Bongioanni limits himself to noting the Greek origin of the given name and its meaning of "protector" or "defender". The source identified as Alessandria specifies that the etymon passes through the Late Latin Alexius, taken from the Greek Alexios or Alexis, and does not rule out that the surname may also be related to Greek personal names such as Alexandros or Alexarchos.

V. Blunda provides the most detailed historical and cultural context: he characterises the surname as Sicilian and places it within the rich Eastern Christian anthroponymic heritage. He notes that the name Alèxios had an especially notable diffusion in the Byzantine Empire —several emperors bore that name, in particular within the Komnenos dynasty during the 11th and 12th centuries— and that its survival in the onomastics of Sicily reflects the cultural prestige of Constantinople on the island.

F. De Laurentiis indicates that Alessio is a variant of the surname Alessi.