AIMS: To explore the causal relationship between physical activity (PA) and the progression of Parkinson's disease (PD), we conducted a two-sample Mendelian randomization (MR) analysis. METHODS: Genetic variants were obtained from publicly available genome-wide association study (GWAS) summary statistics for PA (N = 377,000), age at onset (N = 28,568), and PD progression (N = 4093). Causal estimates were calculated using the inverse variance weighted (IVW) method, with MR-Egger and weighted median analyses performed to assess the robustness of the results. RESULTS: Genetically predicted accelerometer-based overall acceleration average (OAA) was associated with a reduced risk of constipation in PD progression (OR: 0.60, 95% CI: 0.42-0.86, p = 5.50 × 10 CONCLUSION: Our findings suggest a negative causal relationship between PA and PD progression, highlighting the potential role of physical activity in guiding therapeutic strategies for PD management.