The objective of the present review is to evaluate the possible association between phenolic compounds and cardiovascular disease, proposing that their regular consumption in Western diets could be beneficial for protecting patients against cardiovascular disease. An extensive research of scientific literature was performed in the following electronic specialized databases (PubMed central (PMC)-NBCI, Elsevier Journal, Scielo Spain, Scirus, Science Direct, Web of Science), including studies in animals, cells, and humans, to establish the effect of polyphenols in the prevention and development of cardiovascular disease was conducted. The in vitro, animal and human studies show the potential ability of polyphenols to act against cardiovascular disease as a result of their antioxidant effect and vasodilatation and their capacity to improve lipid profile while reducing the concentration of low-density lipoproteins. Polyphenols consumption in Western diets could be beneficial for protecting patients against cardiovascular disease.