Atherosclerotic cardiovascular disease is currently the leading cause of death worldwide. Its pathophysiological basis includes endothelial dysfunction, macrophage activation, vascular smooth muscle cell (VSMC) proliferation, lipid metabolism, platelet aggregation, and changes in the gut microbiota. Salidroside has beneficial effects on atherosclerosis through multiple pathways. In this review, we present studies on the regulatory effect of salidroside on atherosclerosis. Furthermore, we report the protective effects of salidroside against atherosclerosis by ameliorating endothelial dysfunction, suppressing macrophage activation and polarization, inhibiting VSMC proliferation, adjusting lipid metabolism, attenuating platelet aggregation, and modulating the gut microbiota. This review provides further understanding of the molecular mechanism of salidroside and new ideas for atherosclerosis management.