Xanthine oxidase is a crucial enzyme in the regulation of uric acid, with elevated levels leading to gout and hyperuricemia. To combat these conditions, a synergistic approach using antioxidants and xanthine oxidase inhibitors presents a promising treatment strategy. Given the side effects of synthetic inhibitors, this study explores the natural xanthine oxidase inhibitory and antioxidant properties of Sesbania grandiflora leaves extract. The analysis revealed a significant free radical inhibition rate of 61.59 ± 0.90% at a concentration of 100 μg/mL. The SC₅₀ value for the leaves extract was 16.59 ± 0.67 μg/mL, compared to 7.76 ± 0.23 μg/mL for gallic acid, a positive control. The leaves extract also demonstrated notable efficiency in inhibiting uric acid formation, with an IC₅₀ value of 0.36 ± 0.341 μg/mL, although this was higher than the 0.01 ± 0.005 μg/mL value for allopurinol. A strong correlation (r = 0.9958) was found between the antioxidant activity and xanthine oxidase inhibition of the extract, underscoring its effectiveness. This study is the first to report the combined effects of xanthine oxidase inhibition and antioxidant activity in Sesbania grandiflora, highlighting its potential as a natural treatment for gout and related diseases.