Atherosclerosis (As) serves as the pathological basis of various cardiovascular and cerebrovascular diseases. The pathogenesis of As involves intricate and interconnected pathological mechanisms, in which multiple molecular pathways interact synergistically via complex crosstalk to collectively drive disease initiation and progression. Traditional Chinese medicine (TCM) compounds exhibit unique advantages in the prevention and treatment of As by modulating multiple pathological processes, including vascular endothelial function, lipid metabolism, immune and inflammatory responses, oxidative stress, gut microbiota, extracellular vesicles, and macrophage autophagy. Based on the pathological mechanisms of As, this article systematically elucidates the characteristics of TCM compounds in prevention and treatment of As, aiming to provide more comprehensive theoretical evidence for As research and intervention.