Polyphenols is a major group of non-nutrients, considering their diversity, occurrence, and biological properties. Polyphenols play essential roles in the prevention of chronic diseases through the mitigation of inflammation, commonly referred to as meta-flammation. Inflammation is the most common feature of chronic diseases such as cancers, cardiovascular disorders, diabetes, and obesity. This aim of this review was to present a wide spectrum of literature data, including the current understanding of the role of polyphenols in the prevention and management of chronic diseases and their ability to interact with other food compounds in food systems. The publications cited are based on animal models, cohort studies, case controls, and feeding experiments. The significant effects of dietary polyphenols in cancers and cardiovascular diseases are evaluated. The interactive possibilities of dietary polyphenols with other dietary food compounds in food systems and their effects are also presented. However, despite several works, estimation of dietary intake is still inconclusive and a major challenge.