Heart and blood vessels disorders comprise one of the main causes of death worldwide. Pharmacologically active natural compounds have been used as a complementary therapy in cardiovascular disease around the world in a traditional way. Dietary, natural bioactive compounds, as well as healthy lifestyles, are considered to prevent coronary artery diseases. Pre-clinical and clinical studies reported that consumption of plant-food bioactive derivatives including polyphenolic compounds, peptides, oligosaccharides, vitamins, unsaturated fatty acids possess protective effects on cardiovascular diseases. This review aims to summarize the cardiovascular risk factors, pre-clinical studies and clinical trials related to cardioprotective properties of the plant-food-derived bioactive compounds. Molecular mechanisms by the natural bioactive compounds exert their cardiovascular protective properties have also been highlighted.