Atherosclerosis is a chronic, progressive disease caused by damage to blood vessels. Kanglexin (KLX), quercetin, melatonin, tanshinone IIA and other natural drugs play an important role in the process of cell growth, differentiation and proliferation, and have been proven to have an important impact on the regulation of cardiovascular diseases in recent years. In recent years, they have been proven to have an important influence on the regulation of cardiovascular diseases, and it has been discovered that natural products and specific compounds have high value in the treatment of cardiovascular diseases. This article reviews the potential therapeutic potential of these drugs for atherosclerosis by regulating key signaling pathways such as PDGFR-β, JAK2/ STAT3, and PPARδ, as well as by influencing mitochondrial function and antioxidant effects. It provides scientific basis for preventing and treating cardiovascular diseases through natural drugs and offers a new idea for the selection of drugs for treating cardiovascular diseases.