OBJECTIVE: Metabolomics technology has been widely utilized to uncover the action mechanisms of Parkinson's Disease (PD) and to identify PD-related biomarkers. In this study, we compared plasma and fecal metabolite levels between PD patients and their healthy spouses (HS), aiming to identify the associations of differential metabolites with intestinal inflammation, intestinal barrier function, and clinical characteristics of PD. METHODS: Untargeted metabolomics techniques were used to characterize plasma and fecal metabolite profiles. We identified metabolites with elevated plasma levels in PD patients, while no significant differences were observed in fecal samples. Partial correlation analysis was employed to investigate the associations between these metabolites, markers of intestinal inflammation (calprotectin and lactoferrin), markers of intestinal permeability (α-1-antitrypsin and zonulin), and clinical characteristics of PD patients. RESULTS: The study identified ten metabolites that were significantly elevated in the plasma of PD patients compared to HS (p < 0.05), while their fecal concentrations did not differ significantly. Correlation analysis revealed that elevated levels of differential metabolites in the plasma of PD patients were associated with increased intestinal permeability and inflammation. Furthermore, five metabolites, including 3,4-Dihydroxyphenylglycol O-sulfate and Propyl gallate, were linked to PD symptoms. Receiver Operating Characteristic (ROC) curves demonstrated that these metabolites could effectively distinguish between PD patients and HS, with an area under the curve (AUC) of 0.94, indicating excellent predictive performance. CONCLUSIONS: This study identified significant metabolite alterations in PD patients and revealed their associations with intestinal barrier dysfunction and clinical characteristics of the disease.