Atherosclerosis is a common form of cardiovascular disease, which is one of the most prevalent causes of death worldwide, particularly among older individuals. Surgery is the mainstay of treatment for severe stenotic lesions, though the rate of restenosis remains relatively high. Current medication therapy for atherosclerosis has limited efficacy in reversing the formation of atherosclerotic plaques. The search for new drug treatment options is imminent. Some potent medications have shown surprising therapeutic benefits in inhibiting inflammation and endothelial proliferation in plaques. Unfortunately, their use is restricted due to notable dose-dependent systemic side effects or degradation. Nevertheless, with advances in nanotechnology, an increasing number of nano-related medical applications are emerging, such as nano-drug delivery, nano-imaging, nanorobots, and so forth, which allow for restrictions on the use of novel atherosclerotic drugs to be lifted. This paper reviews new perspectives on the targeted delivery of nanoparticles to blood vessels for the treatment of atherosclerosis in both systemic and local drug delivery. In systemic drug delivery, nanoparticles inhibit drug degradation and reduce systemic toxicity through passive and active pathways. To further enhance the precise release of drugs, the localized delivery of nanoparticles can also be accomplished through blood vessel wall injection or using endovascular interventional devices coated with nanoparticles. Overall, nanotechnology holds boundless potential for the diagnosis and treatment of atherosclerotic diseases in the future.