To analyze the correlation between oxidative stress response and cognitive function in patients with vascular Parkinson's syndrome (VPS). Methods: A total of 64 patients with VPS were enrolled in the VPS group, 64 patients with Parkinson's disease (PD) admitted to the hospital during the same period were selected as the PD group, and 64 healthy individuals undergoing physical examinations during the same period were included as the healthy control group. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) scale. Oxidative stress indicators [superoxide dismutase (SOD) and malonaldehyde (MDA)] and MoCA scores were measured and compared among the three groups. The VPS group was further divided into an early subgroup (29 patients) and a middle-to-late subgroup (35 patients) based on Hoehn-Yahr (H-Y) staging, and into a cognitive impairment subgroup (44 patients) and a non-cognitive impairment subgroup (20 patients) based on MoCA scores. Pearson correlation analysis was conducted to assess the relationship between serum SOD, MDA, and MoCA scores. Receiver Operating Characteristic (ROC) curves were plotted to analyze the predictive value of SOD and MDA for cognitive impairment. Univariate and multivariate Logistic regression analyses were performed to identify risk factors for cognitive impairment in VPS patients. Results: The VPS group had higher serum MDA levels than the PD and healthy control groups (P<0.05), and lower serum SOD levels and MoCA scores than the PD and healthy control groups (P<0.05). The middle-to-late subgroup had higher serum MDA levels than the early subgroup (P<0.05) and lower serum SOD levels and MoCA scores than the early subgroup (P<0.05). The cognitive impairment subgroup had higher serum MDA levels than the non-cognitive impairment subgroup (P<0.05) and lower serum SOD levels than the non-cognitive impairment subgroup (P<0.05). Pearson correlation analysis showed a significant positive correlation between serum SOD levels and MoCA scores (r=0.398, P<0.001) and a significant negative correlation between serum MDA levels and MoCA scores (r=－0.432, P<0.001). The area under the ROC curve for combined detection of SOD and MDA in predicting cognitive impairment was 0.811 (95% CI: 0.727～0.954), with sensitivity (93.28%) and specificity (90.17%) higher than those of SOD (76.67%, 74.09%) and MDA (74.28%, 71.46%) alone (P<0.05). Age, hyperuricemia, serum homocysteine (Hcy) levels, cerebral infarction location, cerebral infarction size, microbleeds, SOD, and MDA were identified as risk factors for cognitive impairment in VPS patients (P<0.05). Conclusion: VPS patients exhibit abnormally high serum MDA levels and abnormally low serum SOD levels, which are associated with their cognitive function. Combined detection of MDA and SOD can improve the predictive accuracy for cognitive impairment in VPS patients.