Hyperuricemia (HUA), or elevated uric acid in the blood, has become more prevalent in recent years. Polyphenols, which are known to have good inhibitory activity on xanthine oxidoreductase (XOR), are effective in uric acid reduction. In this review, we address the structure–activity relationship of flavonoids that inhibit XOR activity from two perspectives: the key residues of XOR and the structural properties of flavonoids. Flavonoids’ inhibitory effect is enhanced by their hydroxyl, methoxy, and planar structures, whereas glycosylation dramatically reduces their activity. The flavonoid structure–activity relationship informed subsequent discussions of the changes that occur in polyphenols’ XOR inhibitory activity during their extraction, processing, gastrointestinal digestion, absorption, and interactions. Furthermore, gastrointestinal digestion and heat treatment during processing can boost the inhibition of XOR. Polyphenols with comparable structures may have a synergistic effect, and their synergy with allopurinol thus provides a promising future research direction.

Hyperuricemia, a disorder of purine metabolism associated with cardiovascular disease, gout, and kidney disease, can be alleviated by food-derived peptides. However, the precise mechanisms remain unclear, hindering their development. This study reviews uric acid-lowering peptides from various sources, focusing on two pathways: inhibiting uric acid production and promoting excretion. Low-molecular-weight peptides (<1000 Da) exhibited superior uric acid-lowering effects. We further explored the relationships between amino acid composition and their target interactions. Peptides rich in cyclic amino acids (tryptophan, phenylalanine, and histidine) and containing small amounts of linear amino acids (leucine, cysteine, and glycine) demonstrated significant potential for lowering uric acid. These findings provide theoretical support for developing novel functional foods for the management of hyperuricemia.