Atherosclerosis is an inflammatory vascular disease that is characterized by progressive accumulation of cholesterol in the arterial walls and it is a major cause of cardiovascular disease. Issues related to the side effects of synthetic drugs have in recent times, led to the misuse of drugs, a lack of patient consultations, and consequently, a disruption in meticulous disease control. Therefore, a new insight into medicinal plants has recently emerged and much research has been conducted on these herbs in an attempt to prepare novel naturally based drugs. The aim of this review article was to scrutinize the molecular mechanisms of medicinal plants possessing effectiveness against atherosclerosis. To conduct the review, electronic searches were performed to retrieve potentially relevant publications, indexed within internet databases and reference textbooks concerning the effects and underlying molecular mechanisms of plants or their constituents used to treat atherosclerosis. Overall, medicinal plants facilitate atherosclerosis treatment through a variety of mechanisms which include the regulation of expression of inflammatory factors, stimulation of peroxisome proliferator-activated receptors (PPARs), inhibition of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMG-CoA reductase), promotion of ATP-binding cassette transporter A1 (ABCA1) as well as ATP-binding cassette transporter G (ABCG), facilitation of adiponectin activity, reduction of sterol regulatory element-binding proteins (SREBPs) and antioxidant activity. An increased perception of these herbal mechanistic links is an important prelude to the design of novel plant based drugs.