Atherosclerosis is the leading cause of cardiovascular disease worldwide, posing not only a significant threat to cardiovascular health but also impairing the function of multiple organs, with severe cases potentially being life-threatening. Consequently, the effective treatment of atherosclerosis is of paramount importance in reducing the mortality associated with cardiovascular diseases. With the advancement of nanomedicine and a deeper understanding of the pathological mechanisms underlying atherosclerosis, nanomaterials have emerged as promising platforms for precise diagnosis and targeted therapeutic strategies. These materials offer notable advantages, including targeted drug delivery, enhanced bioavailability, improved drug stability, and controlled release. This review provides an overview of the mechanisms underlying atherosclerotic plaque development and examines nanomaterial-based therapeutic approaches for managing atherosclerotic plaques, including therapies targeting cholesterol metabolism, anti-inflammatory strategies, macrophage clearance, and immunotherapy. Additionally, the paper discusses the current technical challenges associated with the clinical transformation of these therapies. Finally, the potential future integration of nanomaterials, smart nanomaterials, and artificial intelligence in the treatment of atherosclerosis is also explored.