Polyphenols are a structurally diverse class of plant-derived secondary metabolites increasingly recognized for their relevance to both food quality and human health, their classical role as antioxidants, polyphenols influence the sensory attributes of foods, contribute to preservation through antimicrobial and antioxidative actions, and interact with food matrices and processing conditions to shape their stability and bio-accessibility. In human physiology, polyphenols undergo extensive metabolism, particularly by the gut microbiota, generating bioactive metabolites that may mediate systemic effects. This review synthesizes current knowledge on polyphenol chemistry, major dietary sources, and intake patterns; highlights technological applications in food systems, including extraction methods, incorporation into active packaging, and fortification strategies; and summarizes evidence from epidemiological, clinical, and mechanistic studies linking polyphenol exposure to cardiometabolic, neurocognitive, musculoskeletal, and gut-related outcomes. Mechanisms governing bioavailability and host–microbe co-metabolism are discussed, alongside key challenges such as standardized dosing, reliable biomarkers of intake and effect, and scalable strategies for retaining activity in processed foods. Future research integrating food science, microbiome biology, and clinical nutrition is needed to translate polyphenol science into effective, evidence-based innovations for human health.
