The surname Mandrile is typically Piedmontese, originating specifically in the Cuneo area, including localities such as Centallo, Cervasca and Fossano. It could derive from the French nickname mandrillon, which was applied to people who were badly dressed and of unkempt appearance.

Alternatively, its origin could lie in the Franco-Occitan term mandrille, which means straccio or cencio, referring thus to a nickname describing the state or condition of the clothing of the founder of the family. Straccio and cencio are Italian terms for a piece of old or worn cloth, generally used for cleaning or for household tasks. In a more figurative sense, these terms can also describe something in poor condition or of little value.

Another theory holds that it would derive from the word mandria ("herd") plus the suffix -ile of belonging, frequent with the names of animals (canile, ovile, porcile, and so on). The word, very common in place names, alludes to enclosures for the keeping of livestock.

In sum, Mandrile is associated specifically with the province of Cuneo.

• Mandrelli, although very rare, appears to originate in a region taking in Rimini, Pesaro and Perugia.
• Mandrilli, extremely rare, appears to come from lower Piedmont.