Parkinson’s disease (PD) is a prevalent neurodegenerative disorder accompanied by movement disorders and neuroinflammatory injury. Anti-inflammatory intervention to regulate oxidative stress in the brain is beneficial for managing PD. However, traditional natural antioxidants have failed to meet the clinical treatment demands due to insufficient activity and sustainability. Herein, Cu-doping zeolite imidazolate framework-8 (ZIF-8) nanozyme is designed to simulate Cu/Zn superoxide dismutase (SOD) by biomimetic mineralization. The nanozyme composite is then integrated into thermosensitive hydrogel (poly (lactic-co-glycolic acid)-poly (ethylene glycol)-poly (lactic-co-glycolic acid) (PLGA-PEG-PLGA)) to form an effective antioxidant system (Cu-ZIF@Hydrogel). The thermosensitive hydrogel incorporating nanozymes demonstrate distinct viscoelastic properties aimed at enhancing local nanozyme adhesion, prolonging nanozyme retention time, and modulating antioxidant activity, thus significantly improving the bioavailability of nanozymes. At the cellular and animal levels of PD, we find that Cu-ZIF@Hydrogel bypass the blood-brain barrier and efficiently accumulate in the nerve cells. Moreover, the Cu-ZIF@Hydrogel significantly alleviate the PD’s behavioral and pathological symptoms by reducing the neuroinflammatory levels in the lesion site. Therefore, the hydrogel-incorporating nanozyme system holds great potential as a simple and reliable avenue for managing PD.