Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra and striatum, leading to debilitating motor symptoms. Emerging evidence suggests a significant role of neuroinflammation in PD pathogenesis, particularly through the upregulation of inflammatory cytokines. However, the causal relationship between inflammatory mediators and PD remains unclear. This study employs a bidirectional Mendelian randomization (MR) approach to investigate the potential causal associations between circulating levels of 91 inflammatory cytokines and PD. Genetic variants from genome-wide association studies (GWAS) were utilized as instrumental variables to assess the causal impact of PD on specific inflammatory markers, including CD6, IL-17A, and TNFRSF9. Our findings demonstrate that genetically increased levels of CD6, IL-17A, and TNFRSF9 are significantly associated with an elevated risk of PD. Specifically, CD6 was found to be linked with T-cell activation and immune responses in the central nervous system, while IL-17A was implicated in exacerbating neuroinflammation and dopaminergic neuron loss. TNFRSF9, a member of the tumor necrosis factor receptor family, showed associations with cognitive decline in long-term PD progression. These results underscore the critical role of immune-mediated pathways in PD development and suggest that targeting inflammatory cytokines may offer new therapeutic avenues for disease management. The robustness of our results is supported by extensive sensitivity analyses, including inverse variance weighting, MR-Egger, and MR-PRESSO models. Our study provides strong evidence for the involvement of specific inflammatory markers in PD etiology and highlights the need for further research to explore these pathways in diverse populations.