Objective To investigate the serum levels of cystatin C （CysC） and homocysteine （Hcy） in patients with Parkinson’s disease （PD） and their role in evaluating white matter lesions.Methods A retrospective analysis was performed for the data of 124 PD patients who were admitted to our hospital from December 2017 to December 2019 （study group） and 115 healthy volunteers who underwent physical examination in our hospital during the same period of time （control group）.Results Compared with the control group， the study group had significantly higher serum levels of CysC （1.37±0.25 mg/L vs 0.89±0.14 mg/L， P<0.05） and Hcy （20.54±3.21 μmol/L vs 14.89±2.18 μmol/L， P<0.05）. In the study group， 35 patients had white matter lesions， with an incidence rate of 28.23%， and compared with the patients without white matter lesions， the patients with white matter lesions had significantly higher serum levels of CysC （1.58±0.29 mg/L vs 1.29±0.22 mg/L， P<0.05） and Hcy （23.32±3.58 μmol/L vs 19.45±3.12 μmol/L， P<0.05）. Age， the course of PD， hypertension， diabetes， serum CysC， and Hcy were all independent risk factors for PD with white matter lesions （P<0.05）. Serum levels of CysC and Hcy had cut-off values of 1.25 mg/L and 21.02 μmol/L， respectively， in evaluating white matter lesions， and the combination of CysC and Hcy had a sensitivity of 100.00% and an area under the ROC curve （AUC） of 0.953 in evaluating PD with white matter lesions， which were significantly higher than the sensitivity and AUC of each index alone （P<0.05）.Conclusions Patients with PD have relatively high serum levels of CysC and Hcy and a high risk of white matter lesions. Serum CysC and Hcy， age， the course of PD， hypertension， and diabetes are related influencing factors， and the combination of serum CysC and Hcy has high performance in evaluating PD with white matter lesions.