Atherosclerosis is an impairment of the artery walls made up of two membrane layers, intima and media. Oxidative stress, hypertension, and hypercholesterolemia are the three main factors that cause atherosclerosis. These conditions are frequently found together and may cause atherogenesis to rapidly occur. The edible genus Pleurotus is commonly known as oyster mushrooms. Pleurotus spp. has been proven to have valuable medicinal attributes. Hence, they have been listed among mushroom nutriceuticals and categorized as both functional foods and medicinal mushrooms. In this review, we report the benefits of Pleurotus spp. for the prevention and treatment of atherosclerosis via reduction of oxidative stress, hypertension, and hypercholesterolemia in terms of the therapeutic compounds responsible. This review revealed that at least ten different types of Pleurotus spp. have been reported to have anti-atherogenic capabilities, with six of them possessing high levels of anti-atherogenic compounds such as ACE inhibitor peptide, ergothioneine, chrysin, and lovastatin. Hence, it has been demonstrated that Pleurotus spp. has great potential for use as food or extracts from fruiting bodies or mycelium in an alternative therapy for atherosclerosis, through prevention and treatment of oxidative stress, hypertension, and hypercholesterolemia.