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Mango and its by-products have traditional medicinal uses. They contain diverse bioactive compounds offering numerous health benefits, including cardioprotective and metabolic properties. This study aimed to explore the impact of mango fruit and its by-products on human health, emphasizing its metabolic syndrome components. PUBMED, EMBASE, COCHRANE, and GOOGLE SCHOLAR were searched following PRISMA guidelines, and the COCHRANE handbook was utilized to assess bias risks. In vivo and in vitro studies have shown several benefits of mango and its by-products. For this systematic review, 13 studies met the inclusion criteria. The collective findings indicated that the utilization of mango in various forms—ranging from fresh mango slices and mango puree to mango by-products, mango leaf extract, fruit powder, and mangiferin—yielded many favorable effects. These encompassed enhancements in glycemic control and improvements in plasma lipid profiles. Additionally, mango reduces food intake, elevates mood scores, augments physical performance during exercise, improves endothelial function, and decreases the incidence of respiratory tract infections. Utilizing mango by-products supports the demand for healthier products. This approach also aids in environmental conservation. Furthermore, the development of mango-derived nanomedicines aligns with sustainable goals and offers innovative solutions for healthcare challenges whilst being environmentally conscious.