Polyphenols, bioactive compounds found in plant-based foods such as coffee, tea, vegetables, and fruits, are believed to offer potential cardiovascular benefits. However, associations between polyphenol intake (total, classes, and individual polyphenols) and cardiovascular disease (CVD) have been inconsistent. Only specific polyphenols found in certain foods consistently show positive effects on heart health. Recent research highlights the antiinflammatory properties of dietary polyphenols in relation to atherosclerosis, type 2 diabetes, cancer, and mortality. A systematic review revealed varied effects of flavonoid consumption on inflammation, depending on the polyphenol source and high-risk populations. Differences in polyphenol bioavailability, due to interactions with proteins, may explain inconsistent findings between in vitro, in vivo, and clinical studies. Additionally, polyphenol effects on healthy individuals or those with low-to-moderate cardiovascular risk may differ from those with metabolic syndrome. This chapter explores the relationship between polyphenol intake and cardiovascular disease at the population level.