Atherosclerosis (AS) is a chronic inflammatory disease resulting from dysregulated lipid metabolism, constituting the pathophysiological foundation of cardiovascular and cerebrovascular diseases. AS has a high incidence rate and mortality rate worldwide. As such, traditional Chinese medicine (TCM) has been widely used recently due to its stable therapeutic effect and high safety. Ganoderma lucidum polysaccharides (GLP) are the main active ingredients of Ganoderma lucidum, a Chinese herbal medicine. Research has also shown that GLP has anti-inflammatory and antioxidant properties, regulates gut microbiota, improves blood glucose and lipid levels, and inhibits obesity. Most of the current research on GLP anti-AS is focused on animal models. Thus, its clinical application remains to be discovered. In this review, we combine relevant research results and start with the pathogenesis and risk factors of GLP on AS, proving that GLP can prevent and treat AS, providing a scientific basis and reference for the future prevention and treatment of AS with GLP.