Aims: To investigate the effect of GAS in PD models by regulating ferroptosis and cell senescence. Methods: MPTP or MPP+ was used to establish PD models in vivo or in vitro, and the effect of GAS was detected by behavioral analysis, immunohistochemistry and cell viability. At the same time, transmission electron microscopy, biochemical kits, Western blotting, immunofluorescence, and molecular docking were used. Results: We found that gastrodin could inhibit cell senescence in PD models. In addition, GAS was found to inhibit ferroptosis, regulate oxidative stress level, and level of ACSL4, FTH1, SLC7A11, GPX4. We also found that Ferrostatin-1 and GAS could inhibit cell senescence. The results of molecular docking and immunofluorescence showed that p53 may be an important target of GAS. After treatment with Pifithrin-α, the protective effect of GAS was enhanced. Conclusion: GAS inhibits cellular senescence in PD models and treats PD through a novel mechanism related to ferroptosis.