Atherosclerosis (As) is the main cause of coronary heart disease, stroke and peripheral vascular disease. Nowadays, there are many theories to explain its pathogenesis, but none of them has clarified the specific pathogenesis. Anti-platelet aggregation, lipid-lowering, anticoagulation and thrombolysis are the main clinical drugs treatment at present, but they have little effect on the protection of vascular endothelium and have poor specificity. The traditional Chinese medicine salidroside (SAL) has significant anti-As effect in animal model experiments. A large number of mechanism studies have also confirmed that SAL can significantly reduce vascular endothelial cell injury, inhibit endothelial apoptosis, delay endothelial senescence, inhibit inflammation and stress response, prevent foam cell formation and the occurrence of apoptosis, prevent vascular smooth muscle cells from overproliferation, reduce blood viscosity, prevent thrombosis and stabilize plaque, thereby protecting the vascular system and inhibiting the occurrence and development of As. Therefore, SAL is expected to become an important treatment for preventing the entire process of As from occurrence, development to deterioration. This article summarizes the research progress of the mechanism of SAL intervening As in recent years, aiming to provide reference value for further research and clinical application.