| Date: | 5–11 April |
| Edition: | 2nd |
| Surface: | Clay |
| Location: | Oeiras, Portugal |
| Champs: |  Pedro Cachin |
| Champd: | Nuno Borges / Francisco Cabral |
| Before Name: | Open de Oeiras |
| Before Year: | 2021 |
| Main Name: | Open de Oeiras |
| After Name: | Open de Oeiras III |
| After Year: | 2021 |
The 2021 Open de Oeiras II was a professional tennis tournament played on clay courts. It was the second edition of the tournament, part of the 2021 ATP Challenger Tour. It took place in Oeiras, Portugal between 5 and 11 April 2021.
| Country | Player | Rank1 | Seed | |
|---|---|---|---|---|
| Oscar Otte | 154 | 1 | ||
 France | Enzo Couacaud | 185 | 2 | |
| Ernesto Escobedo | 205 | 3 | ||
 Morocco | Elliot Benchetrit | 240 | 4 | |
 Italy | Gian Marco Moroni | 241 | 5 | |
| Argentina | Marco Trungelliti | 247 | 6 | |
 Spain | Nicola Kuhn | 250 | 7 | |
| France | Tristan Lamasine | 257 | 8 |
The following players received wildcards into the singles main draw:
The following player received entry into the singles main draw as a special exempt:
The following players received entry into the singles main draw as alternates:
The following players received entry from the qualifying draw:
See main article: 2021 Open de Oeiras II – Singles.
Pedro Cachin def. Nuno Borges 7–6(7–4), 7–6(7–3).See main article: 2021 Open de Oeiras II – Doubles.
Pavel Kotov / Tseng Chun-hsin 6–1, 6–2.
