BACKGROUND: Hyperuricemia is associated with several metabolic and cardiovascular disorders, and traditional treatments, such as xanthine oxidase (XO) inhibitors, often have limitations, such as severe hypersensitivity reactions or ineffectiveness in achieving target serum urate levels in some patients. Quercetin, a naturally occurring flavonoid, has shown potential as a hypouricemic agent through XO inhibition. OBJECTIVE: This study aims to evaluate the potential hypouricemic effect of Quercetin Phytosome™ (QP) supplementation across three cohort studies involving healthy adults with various metabolic health profiles, exploring its potential as a safe, effective intervention for hyperuricemia. METHODS: Clinical data collected in various clinics in Italy between September 2021 and April 2024 under real-life clinical settings from three distinct cohort studies, were analyzed. Cohort 1 consisted of 164 healthy participants (87 QP-treated, 77 probiotic RESULTS: In Cohort 1, QP significantly reduced uric acid levels by 15.2% in males and 13.8% in females, with no significant changes observed in the probiotic group. Cohort 2 showed a significant 13.1% reduction in uric acid ( CONCLUSION: QP supplementation demonstrates a significant hypouricemic effect. Additionally, triglyceride-lowering benefits were evident, particularly in metabolically compromised individuals (Cohorts 2 and 3), where these effects were statistically significant. With high tolerability, these findings highlight Quercetin Phytosome™'s potential as a safe adjunctive therapy for hyperuricemia management, meriting further investigation in larger, randomized trials to confirm its efficacy and safety. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov, identifier NCT06652035.