Abstract <p>We aimed to explore the correlation of methionine (Met)/homocysteine (Hcy) ratio (MHR) with cerebral small vessel disease (CSVD)-related vascular cognitive impairment (VCI), and to assess its predictive value in B-complex vitamin intervention. This study enrolled 268 CSVD patients for cross-sectional analysis. Additionally, multivariate Logistic regression and receiver operating characteristic (ROC) curve analyses were implemented to investigate the prediction efficiency. Next, 12-week B-complex vitamin intervention (folic acid 5 mg/day, vitamin B6 50 mg/day, and vitamin B12 500 µg/day) was conducted on 86 patients to assess variations in MHR and cognitive function before and after intervention. Gradual increments in the Montreal Cognitive Assessment (MoCA) score (<i>P</i> &lt; 0.001) and significant decrements in the white matter hyperintensity (WMH) and total CSVD score (<i>P</i> &lt; 0.01) were observed with the elevation of MHR quartiles. MHR served as an independent protective factor against VCI [odds ratio (OR) = 0.44, <i>P</i> = 0.002]. After intervention, Hcy declined (<i>P</i> &lt; 0.001), while MHR (<i>P</i> &lt; 0.001) and MoCA score rose (<i>P</i> = 0.002). A positive association was observed between ΔMHR and ΔMoCA score (<i>r</i> = 0.46, <i>P</i> &lt; 0.001), and the low baseline MHR group displayed more obvious improvements in cognitive function (<i>P</i> &lt; 0.001). MHR has a close correlation with cognitive function and imaging impairment in CSVD patients. MHR acts as an independent protective factor against VCI and outperforms Hcy in prediction efficiency. The 12 weeks of B-complex vitamin intervention leads to significantly reduced Hcy, elevated MHR, and improved cognitive state.</p>