The 2021 Internazionali Femminili di Palermo was a professional women's tennis tournament played on outdoor clay courts at the Country Time Club.

It was the 29th edition of the tournament and part of the 2021 WTA Tour.

First-seeded Danielle Collins won the singles title.

[1] Danielle Collins defeated Elena-Gabriela Ruse, 6–4, 6–2.

The following players received wildcards into the main draw: The following player received entry using a protected ranking: The following players received entry from the qualifying draw: The following pairs received wildcards into the doubles main draw: