| 1. Round | 28/08/2021 | Twente/Heracles [U21] | - | Almere City FC [U21] | 1:2 |  |
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| 2. Round | 11/09/2021 | NEC Nijmegen [U21] | - | Twente/Heracles [U21] | 2:1 | ||||
| 3. Round | 18/09/2021 | Twente/Heracles [U21] | - | NAC Breda [U21] | 5:2 | ||||
| 4. Round | 25/09/2021 | Feyenoord [U21] | - | Twente/Heracles [U21] | 2:0 | ||||
| 5. Round | 02/10/2021 | Twente/Heracles [U21] | - | ADO Den Haag [U21] | 0:0 | ||||
| 6. Round | 16/10/2021 | Twente/Heracles [U21] | - | FC Groningen [U21] | 1:2 |  |
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| 7. Round | 23/10/2021 | sc Heerenveen [U21] | - | Twente/Heracles [U21] | 0:3 | ||||
| 8. Round | 30/10/2021 | ADO Den Haag [U21] | - | Twente/Heracles [U21] | 3:1 | ||||
| 9. Round | 06/11/2021 | Twente/Heracles [U21] | - | Feyenoord [U21] | 0:3 | ||||
| 10. Round | 20/11/2021 | NAC Breda [U21] | - | Twente/Heracles [U21] | 3:1 | ||||
| 11. Round | 04/12/2021 | Twente/Heracles [U21] | - | NEC Nijmegen [U21] | 1:1 | ||||
| 14. Round | 18/12/2021 | FC Groningen [U21] | - | Twente/Heracles [U21] | 6:1 |
Netherlands