BACKGROUND:Hyperuricemia, a prevalent chronic metabolic disorder caused by purine metabolism disturbances, is characterized by elevated serum uric acid (UA) levels. Prolonged hyperuricemia can cause severe complications such as gout or kidney damage. However, the toxic side effects of and adverse reactions to UA-lowering drugs are becoming increasingly prominent. Therefore, new targets and drugs for hyperuricemia are needed. PURPOSE:This review aims to summarize recent research progress on the prevention and treatment mechanisms for gut microbiota-hyperuricemia from the perspective of plant-derived natural products. METHODS:Data from PubMed, Web of Science, ScienceDirect, and the CNKI databases spanning from January 2020 to December 2024 were reviewed. The aim of this study is to categorize and summarize the relevant mechanisms through which natural products improve hyperuricemia via the gut microbiota. The retrieved data followed PRISMA criteria (Preferred Reporting Items for Systematic reviews and Meta-Analyses). RESULTS:Regulating gut microbiota as a treatment for hyperuricemia. Targeting the gut microbiota could reduce host UA levels by promoting purine degradation, reducing UA production, and increasing UA excretion. Moreover, the gut microbiota also exerts anti-inflammatory and antioxidant effects that alleviate complications such as renal damage caused by hyperuricemia. Due to their diverse sources, multicomponent synergy, multitarget effects, and minimal side effects, plant-derived natural products have been extensively utilized in the management of hyperuricemia. Especially, utilizing natural products from plants to regulate the gut microbiota has become a new strategy for reducing UA levels. CONCLUSION:This review comprehensively summarizes recent advances in understanding the preventive and therapeutic mechanisms of plant-derived natural products in ameliorating hyperuricemia and its comorbidities through gut microbiota modulation. This review contributes a novel perspective for the development of safer and more efficacious UA-lowering products.