The genus Mangifera (Anacardiaceae) is widely distributed across most tropical and subtropical regions and has long been used in traditional medicine for its nutritional value and for treating aging-related conditions, parasitic infections, diabetes, and dysentery. Nearly every part of the plant, leaves, seeds, fruits, stems, pulp, and peel, has been investigated for various research purposes. These plants have been used therapeutically for decades. Using databases, such as PubMed/MEDLINE, Scopus, EBSCO, Europe PMC, and Google Scholar, all relevant research articles were thoroughly reviewed, with emphasis on pharmacology and bioactive plant constituents. Among all species, Mangifera indica has been the most extensively studied in recent years. Mangiferin is recognized as one of the most potent and widely investigated bioactive compounds in the genus. The phytochemical profile includes flavonoids, terpenoids, alkaloids, tannins, resins, sterols, and other classes of secondary metabolites. Pharmacological findings compiled in this review encompass its antioxidant, anticancer, hepatoprotective, cardioprotective, antiulcer, neuroprotective, antidiabetic, antitumor, antiviral, anti-inflammatory, antiarthritic, and additional biological activities. This study also discusses novel drug-delivery strategies related to the genus, including nanoparticle- based formulations of Mangifera indica and mangiferin. Overall, this review aims to provide an updated overview of developments in the genus Mangifera, covering traditional uses, chemical constituents, pharmacological effects, and therapeutic applications. This comprehensive assessment may offer new perspectives for future research on the genus Mangifera.