Background <p>Neurite Orientation Dispersion and Density Imaging (NODDI) has advanced the study of cortical microstructure. However, its application to participants with cerebral microbleeds (CMBs) to explore cognitive impairment mechanisms and potential imaging biomarkers remains underexplored.</p> Methods <p>This observational study used NODDI to assess cortical microstructural changes in three groups: 52 participants with cerebral small vessel disease and CMBs (CSVD-c), 78 CSVD participants without CMBs (CSVD-n), and 37 healthy controls. Multivariable regression analysis examined the correlation between altered NODDI metrics, CMB severity, and cognitive function. Cox regression analysis evaluated the association between altered NODDI metrics and dementia risk.</p> Results <p>The CSVD-c group showed a significant decrease in Intracellular Volume Fraction (ICVF) in the bilateral caudate nucleus and an increase in Isotropic volume fraction (ISOVF) in the right precuneus compared to both the controls and CSVD-n groups. Decreased ICVF in the bilateral caudate nucleus correlated with the number of CMBs (<i>P</i> = 0.023), lower logical memory scores (<i>P</i> = 0.003), and higher Rey Auditory Verbal Learning Test and Clinical Dementia Rating-Sum of Boxes scores (<i>P</i> = 0.011; <i>P</i> &lt; 0.001). Increased ISOVF in the right precuneus was significantly associated with a higher risk of dementia (<i>P</i> = 0.039), but this significance was lost after adjusting for age, sex and years of education.</p> Conclusion <p>Participants with CMBs exhibit decreased ICVF in the bilateral caudate nucleus and increased ISOVF in the right precuneus, associated with cognitive impairment and increased dementia risk. NODDI metrics may serve as valuable markers for investigating CMB-related cognitive impairment.</p>