The effect of sexual dimorphism on the metabolism of patients with Parkinson's disease has not been clarified. A group of patients with Parkinson's disease and healthy controls were recruited, and their clinical characteristics and plasma were collected. Untargeted liquid chromatography-mass spectrometry-based plasma metabolomics profiling was performed. Differentially expressed metabolites between patients and healthy controls were respectively identified in the male and female participants and metabolite set enrichment analyses were further employed. A total of 75 patients with Parkinson's disease (37 males and 38 females) and 31 healthy controls (16 males and 15 females) were enrolled while no significant differences can be discovered in clinical characteristics. The constructed male-specific metabolic model from orthogonal partial least squares-discriminant analysis can't well recognize female patients and the female-specific model also can't accurately identify male patients. There were 55 differentially expressed metabolites in the male participants, and fatty acids and conjugates and eicosanoids were the significantly enriched metabolite sets. Meanwhile, 86 metabolites were differentially expressed in the female participants while fatty acids and conjugates and glycerophosphocholines were enriched. Only 17 metabolites were simultaneously changed in both male and female patients. Significant sex differences of lipid metabolism were found in patients with Parkinson's disease.