BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are known for their cardiovascular benefits, but their impact on serum uric acid levels is not well understood. This study evaluates the hypouricemic effects of SGLT2is and their potential cardiovascular implications. METHODS: A network meta-analysis was performed, including 56 studies (16,788 participants) contributing data to the meta-analysis. The effects of SGLT2is on serum uric acid levels were analyzed with weighted mean difference (WMD) as the effect estimate. Bootstrapped meta-analysis, trial sequential analysis, and meta-regression were utilized to validate the findings and assess the influence of covariates. The certainty of the evidence was evaluated. RESULTS: The analysis revealed that SGLT2is significantly reduced serum uric acid levels (WMD: -40.01 μmol/L). Specific reductions were noted for ertugliflozin (-42.17 μmol/L), dapagliflozin (-40.28 μmol/L), empagliflozin (-46.75 μmol/L), canagliflozin (-35.55 μmol/L), and ipragliflozin (-10.48 μmol/L). Both low and high doses were effective, with empagliflozin showing the highest efficacy. No significant associations were found with covariates. The evidence was of moderate certainty. CONCLUSION: SGLT2is significantly lower serum uric acid levels, with empagliflozin being the most effective. These findings suggest a potential role in reducing cardiovascular risk. Further research is needed to explore their effects on hyperuricemic patients, and monitoring serum uric acid levels is recommended.