Abstract: Objective: Given the limitations of current interventions for hyperuricemia and the potential of Eurotium cristatum fermentation to enhance the bioactivity of natural products, this study aimed to investigate the urate-lowering effect and safety of E. cristatum-fermented Taxilli Herba tea, thereby providing experimental evidence for developing efficient, low-toxicity natural urate-lowering agents. Methods: A "pretreatment-synchronous intervention" design was adopted. Mice were first administered fermented Taxilli Herba tea via oral gavage for 5 consecutive days for pretreatment. Subsequently, a hyperuricemia model was established by intraperitoneal injection of hypoxanthinecombined with subcutaneous injection of potassium oxonate, during which the fermented tea was continuously administered for three days. To elucidate its urate-lowering mechanism, serum uric acid (SUA) levels and hepatic xanthine oxidase (XOD) activity were measured. Concurrently, liver and kidney function indices—alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and serum creatinine (SCr)—were assessed to evaluate organ protection. Safety was evaluated via acute toxicity tests (single gavage of maximum concentration, with 14-day observation to determine LD₅₀) and subacute toxicity tests (28-day continuous gavage, with measurements of body weight, hematological, biochemical, and urinary parameters, plus histopathological examination of organs to assess toxic effects). Results: Relative to the blank group, the model group exhibited significantly elevated SUA levels, hepatic XOD activity (P<0.01), and abnormal liver/kidney function indices (ALT, AST, BUN, SCr, P<0.01), confirming successful model establishment with concurrent organ damage. In contrast, all dose groups of fermented Taxilli Herba tea showed significantly reduced SUA levels (P<0.05) and XOD activity (P<0.01) versus the model group, alongside improved liver and kidney function indices (P<0.05 or P<0.01). These findings indicate that the fermented tea reduces urate production by inhibiting XOD activity and exerts protective effects on liver and kidney function. Safety evaluation revealed an oral LD₅₀>10 g/kg·bw in both male and female mice, classifying it as practically non-toxic. After 28-day continuous gavage, no significant abnormalities in body weight, hematological, or biochemical parameters were observed in rats across all dose groups, and no test substance-related histopathological changes were detected in organs. Conclusion: E. cristatum-fermented Taxilli Herba tea exerts a significant urate-lowering effect by inhibiting XOD activity and simultaneously ameliorates hyperuricemia-induced liver and kidney dysfunction. Its "synergistic urate-lowering and organ-protective effects" outperform single-target interventions and present high safety.