Mangifera indica L. (mango) is a rich source of mangiferin, a bioactive compound with diverse therapeutic properties. This study optimized mangiferin extraction from mango leaves using the dynamic maceration method and Box–Behnken design. Four parameters—extraction time, solvent concentration, temperature, and solvent-to-powder ratio—were evaluated. Optimal conditions (66% ethanol, 54°C, 88 min, 1:19 ratio) yielded 50.68 ± 0.65 mg/g of mangiferin. The results highlight the efficiency of dynamic maceration for pharmaceutical and nutraceutical applications.