According to E. De Felice, the surname has as its base the personal name Ulisse, coming from the Latin Ulixes, an adaptation of the Greek Odysseýs (or Olysseýs), corresponding to the Homeric hero and protagonist of the Odyssey. This name, of uncertain etymology, has been linked by tradition —already in Homer— to a verb meaning "to be angry", although this interpretation is not certain. Unlike many other medieval names, Ulisse does not have a hagiographic origin, but it achieved a notable diffusion in Italy from the Renaissance onwards, thanks to the recovery of classical culture. Its use spread especially in central Italy, with a greater presence in the Marche and Lazio, and also in the continental south.

For his part, A. Bongioanni fully agrees with this interpretation, likewise highlighting the classical origin of the name Ulisse and its consolidation in Italian onomastics during the Renaissance. He reiterates its link with the figure of the hero of the Greek tradition and notes, like De Felice, the uncertainty of its etymology and its diffusion mainly in central and southern Italy.