Abstract
Agri-food residues have accumulated globally at unprecedented scales, generating environmental pressures and resource inefficiencies, a core problem addressed in this review, while simultaneously representing rich, underutilized reservoirs of health-promoting phytochemicals. This review synthesizes recent advances (2016-2025) in the green extraction, characterization, and biological validation of phytochemicals from plant-based residues, including polyphenols, flavonoids, carotenoids, alkaloids, and dietary fibers from key sources such as grape pomace, citrus peels, coffee silverskin, pomegranate peel, cereal brans, and tropical fruit by-products. Emphasis is placed on sustainable extraction methods: ultrasound-assisted extraction (UAE), microwave-assisted extraction (MAE), pressurized liquid extraction (PLE), supercritical CO(2) extraction (SFE), and natural deep eutectic solvents (NADES), which enable efficient recovery while minimizing environmental impact. In vitro, in vivo, and clinical studies demonstrate that residue-derived compounds exert antioxidant, anti-inflammatory, metabolic-regulating, and prebiotic effects, contributing to health in general and gut microbiota modulation. Integrating these bioactives into functional foods and nutraceuticals supports sustainable nutrition and circular bioeconomy goals by reducing food waste and promoting health-oriented valorization. Regulatory advances, including approvals from the European Food Safety Authority (EFSA) and the U.S. Food and Drug Administration (FDA) for ingredients such as olive phenolics, citrus flavanones, and coffee cascara, further illustrate increasing translational readiness. The convergence of green chemistry, biorefinery design, and nutritional science positions agri-food residues as pivotal resources for future health-promoting and environmentally responsible diets. Remaining challenges include scaling cost-effective green processes, harmonizing life cycle assessment protocols, expanding toxicological datasets, and conducting longer-term clinical trials to support safe and evidence-based commercialization.