Objective To exploring the correlation of serum alkaline phosphatase （ALP） and amyloid A protein（SAA） levels with cerebral microbleeds （CMBs） in patients with cerebral small vascular disease. Methods The study involved 204 patients with cerebral small vascular disease from the neurology department of Anhui No.2 Provincial People's Hospital. According to whether cerebral microbleeds occurred， they were categorized into a CMBs group（n = 117）and a non-CMBs group（n = 87）. The baseline data of two groups of patients were campared. The risk factors of cerebral microbleeds were identified and the serum ALP and SAA leves in the CMBs group across different degrees and locations were compared. Correlation analysis was used to investigate the correlation between the serum ALP， SAA levels， and the severity of cerebral microbleeds.ROC curves was used to evaluate their diagnostic value for cerebral microbleeds. Results Age， hypertension rate， serum ALP and SAA levels in the CMBs group were higher than those in the non-CMBs group （P < 0.05）. Logistic regression analysis showed that age， hypertension， serum ALP， and SAA levels were independent risk factors for cerebral microbleeds （P < 0.05）. ROC curves showed that the AUC values of serum ALP and SAA alone for predicting cerebral microbleeds were 0.801， 0.813.If in combination， the AUC value was 0.914 which is higher. Correlation analysis showed that the serum ALP and SAA levels were positively correlated with the severity of cerebral microbleeds （P < 0.001）， Meanwhile， there was no statistically significant difference between the serum ALP and SAA levels and different locations of cerebral microbleeds （P > 0.05）. Conclusions Elevated serum ALP and SAA levels in patients with cerebral small vessel disease are closely related to cerebral microbleeds. Early combined detection can effectively predict the risk of cerebral microbleeds.