| 1. Round | 14/08/2021 | 1. FSV Mainz 05 II | - | VfR Aalen | 3:1 |  |
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| 2. Round | 21/08/2021 | FC Gießen | - | 1. FSV Mainz 05 II | 0:1 | ||||
| 3. Round | 25/08/2021 | 1. FSV Mainz 05 II | - | TSV Steinbach Haiger | 2:1 | ||||
| 4. Round | 29/08/2021 | SG Sonnenhof Großaspach | - | 1. FSV Mainz 05 II | 1:3 | ||||
| 13. Round | 16/10/2021 | 1. FSV Mainz 05 II | - | Hessen Kassel | 1:3 | ||||
| 18. Round | 13/11/2021 | 1. FSV Mainz 05 II | - | Bahlinger SC | 3:0 | ||||
| 28. Round | 12/03/2022 | Kickers Offenbach | - | 1. FSV Mainz 05 II | 2:0 | ||||
| 35. Round | 23/04/2022 | TSV Schott Mainz | - | 1. FSV Mainz 05 II | 0:0 |
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Italy