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Mangiferin, a prominent phytochemical found abundantly in mango leaves, possesses a wide range of pharmacological properties, including antioxidant, antiviral, anticancer, and antidiabetic effects (Lee, Kim, & Kim, 2019). However, its minted solubility hinders its pharmaceutical applications. This study aimed to optimize the parameters of the spray-drying process to improve the dissolution of mangiferin in Mangiferin indica L. leaf extract and formulate capsules for diabetes treatment. Fourteen experiments were designed using Design Expert software and optimized with BC Pharsoft OPT software. Three independent variables were investigated: the ratio of mangiferin to excipients (X1), the ratio of maltodextrin in spray fluid composition (X2), and inlet air temperature (X3). The dissolution of mangiferin was measured as the percentage released within 5 minutes (Y1), 15 minutes (Y2), and 30 minutes (Y3), and the percentage of hygroscopicity at 25oC (Y4). The results showed that the optimized spray drying process and formula, which included the ratios of mangiferin and maltodextrin in the spray drying solution of 8.30% and 9.63%, respectively, the inlet air temperature of 156.26oC, blowing speed of 50 m3/s, and pump flow of 3 mL/min, possessed a dissolution of mangiferin in the spray drying powder of 91.89 ± 2.43% at 30 minutes, and a percentage hygroscopicity of 0.13 ± 0.13% at 25oC. This study, for the first time, explored the cause-effect relationships and optimization of the formulation of Mangifera indica L. leaf extract powder. The spray-dried powder capsule released more than 90% mangiferin within 30 minutes and showed significant hypoglycemic effects in inhibiting the a-glucosidase enzyme (IC 50 of 36.94 µg/mL equivalent to mangiferin in comparison with the commercial drug Glucobay (acarbose 176.09 µg/mL). In summary, the capsules containing the optimized formula of mangiferin spray-dried powder from Mangifera indica L. leaf extract have been successfully prepared and have potential antidiabetic effects in in-vitro settings. [ABSTRACT FROM AUTHOR]