Abstract Objective: To explore the correlation between plasma neuropathological proteins and inflammatory factors with constipation in patients with Parkinson‘s disease (PD). Methods: A total of 88 patients with PD were recruited from the Department of Neurology at the Affiliated Huai’an No. 1 People’s Hospital of Nanjing Medical University. Motor and non-motor symptoms were assessed using the Unified Parkinson's Disease Rating Scale (UPDRS), the Hamilton Anxiety Scale (HAMA), the Hamilton Depression Scale (HAMD), and other validated scales. According to the Werner Constipation Score, PD patients were divided into PD patients with constipation (PD-C) and PD patients without constipation (PD-NC). During the same period,30 healthy individuals matched in age and sex were enrolled as the control group (HC). Plasma levels of α-synuclein (α-syn), phosphorylated α-synuclein (p-α-syn), neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), S100 calcium-binding protein B (S100B), tumor necrosis factor-α (TNF-α), interleukin (IL)-18, and IL-1β were measured by ELISA. Statistical analyses were performed using SPSS 29.0 and R software. Group differences were compared using t-tests and Mann-Whitney U tests. Binary logistic regression was used to identify risk factors for constipation, and ROC curves were constructed to evaluate the predictive performance of biomarker combinations based on GFAP. Results: Plasma levels of GFAP, S100B, TNF-α, IL-18, and IL-1β were significantly higher in the PD with constipation group (all P < 0.05). After adjusting for age and lifestyle, multivariate analysis identified GFAP, S100B, and IL-1β as independent risk factors for constipation in PD. The combined predictive model based on these factors exhibited favorable diagnostic performance. Conclusion: Constipation in PD patients may be related to inflammatory reaction mediated by activation of peripheral glial cells.