Abstract: Arteriosclerosis (AS) is a chronic, inflammatory disease closely associated with the development of various cardiovascular diseases and poses a significant threat to human life and health. Programmed Cell Death (PCD) is precisely regulated by multiple genes and pathways, playing a critical role in maintaining cellular homeostasis. Recent evidence underscores the crucial role of endothelial cells (ECs), vascular smooth muscle cells (VSMCs), and macrophages-mediated PCD, encompassing apoptosis, autophagy, pyroptosis, ferroptosis, necroptosis, cuproptosis, and NETosis, in the pathogenesis of AS. Natural products from plants, exhibiting anti-AS properties, have attracted considerable research interest. A wealth of evidence suggests that these natural products, by modulating PCD through various mechanisms, hold great promise in the prevention and treatment of AS. Therefore, this review synthesizes information on the common types of PCD in ECs, VSMCs, and macrophages, and examines how cell-mediated PCD influences different stages of AS. Additionally, highlight recent discoveries in the roles and molecular mechanisms of natural products in modulating PCD to mitigate AS. Drawing on these insights, we underscore the significance of natural drugs in treating AS by targeting PCD, potentially providing a foundation for developing novel anti-AS drugs from natural sources.