The increasing incidence of gout poses a very challenging management problem. However, the currently available drugs often have various toxic side effects. As a traditional edible and medicinal macrofungus, Sanghuangporus vaninii presents high medical research value. Therefore, to improve fermentation efficiency and identify novel anti-gout drugs, we optimized the culture medium of S. vaninii with lignin and further investigated its anti-gout effects. The results indicated that 0.06 g/L of lignin was most favorable for S. vaninii growth. In the hyperuricemia cell model, we found that S. vaninii could significantly induce the downregulation of xanthine oxidoreductase and the upregulation of hypoxanthine-guanine phosphoribosyltransferase. Furthermore, following oral administration of the extracts, the serum uric acid levels of mice with hyperuricemia were effectively reduced. In a gouty arthritis rat model, S. vaninii also achieved strong suppression of synovial swelling, indicating its anti-inflammatory activity. In addition, the antioxidant assays suggested that S. vaninii shows a strong free radical scavenging capacity and can effectively alleviate cellular oxidative stress. This activity further enhances its anti-inflammatory activity and reduces the incidence of comorbidities. In summary, our results provide the basis for the utilization of S. vaninii to develop anti-gout drugs.