Objective:To investigate the changes in cognitive and behavioral function in patients with cerebral small vessel disease and their correlation with serum homocysteine (Hcy) and cystatin C (CysC) levels.Methods:Ninety-four patients with cerebral small vascular disease who received treatment in Zhejiang Xin'an International Hospital from March 2019 to March 2021 were included in the observation group. An additional 80 healthy controls who concurrently received physical examination were included in the control group. The Mini-Mental State Scale (MMSE) and the Montreal Assessment Scale (MoCA) were used to evaluate cognitive function. The activity of daily living (ADL) was used to evaluate behavioral function. Enzyme-linked immunosorbent assay was used to measure serum Hcy and CysC levels. MMSE score, MoCA score, ADL score, serum Hcy and CysC levels were compared between the two groups. The receiver operating characteristic (ROC) curve was used to analyze the sensitivity and specificity of serum Hcy and CysC levels in the diagnosis of cerebral small vessel disease. Pearson correlation analysis was performed to analyze the correlation between serum Hcy and CysC levels and cognitive behavioral function.Results:MMSE score, MoCA score, and ADL score in the observation group were (21.21 ± 2.87) points, (20.18 ± 3.25) points, and (34.32 ± 5.45) points, which were significantly lower than (28.23 ± 1.02) points, (28.45 ± 0.89) points and (76.35 ± 8.29) points in the control group ( t = 20.78, 22.05, 40.03, all P < 0.05). Serum Hcy and CysC in the observation group were (16.28 ± 2.97) μmol/L and (1.21 ± 0.23) mg/L, which were significantly higher than (8.35 ± 1.76) μmol/L and (0.56 ± 0.12) mg/L in the control group ( t = 20.95, 22.77, both P < 0.05). ROC curve analysis showed that the sensitivity and specificity of serum Hcy in diagnosing cerebral small vessel disease were 85.29% and 53.85%, respectively; the sensitivity and specificity of serum CysC in diagnosing cerebral small vessel disease were 81.54% and 41.38%, respectively. Pearson correlation analysis revealed that serum Hcy level was linearly negatively correlated with MMSE score, MoCA score, and ADL score ( r = -0.79, -0.68, -0.71, all P < 0.05); serum CysC level was linearly negatively correlated with MMSE score, MoCA score, and ADL score ( r = -0.67, -0.75, -0.78, P < 0.05). Conclusion:The cognitive and behavioral function of patients with cerebral small vessel disease are decreased, and serum Hcy and CysC levels are increased. Serum Hcy and CysC levels are closely related to the cognitive and behavioral function of patients with cerebral small vessel disease.