The 2021 Giro di Sicilia (known as Il Giro di Sicilia EOLO for sponsorship reasons[1]) was the 25th edition of the Giro di Sicilia road cycling stage race and the second edition since its revival in 2019.

[2] The race was originally scheduled for April but had been postponed due to COVID-19 pandemic restrictions, which had also caused the cancellation of the 2020 edition.

[1][3] Five of the 19 UCI WorldTeams, eight UCI ProTeams, and seven UCI Continental teams made up the 20 teams that participated in the race.

[1][4] Amore & Vita and Zalf Euromobil Fior, with six riders each, were the only teams to not enter a full squad of seven riders.

133 riders started the race, of which 84 finished.