The 2021 Amex-Istanbul Challenger II was a professional tennis tournament played on hard courts.

It was the 35th edition of the tournament which was part of the 2021 ATP Challenger Tour.

It took place in Istanbul, Turkey between 13 and 19 September 2021.

The following players received wildcards into the singles main draw: The following players received entry from the qualifying draw: The following player received entry as a lucky loser: