Mangiferin, a glucosyl xanthone, is a plant metabolite with promising nootropic and ergogenic properties. However, its poor and inconsistent systemic bioavailability limits its therapeutic potential. Additionally, the pharmacokinetics of mangiferin from mango leaf extract formulations remain uncharacterized in humans. This study validated a UHPLC-MS/MS method and conducted a human pharmacokinetic study approved by an ethics committee. The bioavailability of mangiferin and its monosodium salt was assessed from two standardized mango leaf extracts: MLE60, standardized to 60% mangiferin but practically insoluble in water, and MLES, the water-soluble monosodium salt form, also standardized to 60%. Twelve participants (six females) received oral doses of each extract in a crossover design with a 7-day washout period. Plasma analysis showed significantly higher AUC and C