Natural compounds have been known as biosafety agents for their significant clinical and biological activity against dreadful diseases, including cancer, cardiovascular, and neurodegenerative disorders. Gambogic acid (GA), a naturally occurring xanthone-based moiety, reported from Garcinia hanburyi tree, is known to perform numerous intracellular and extracellular actions, including programmed cell death, autophagy, cell cycle arrest, antiangiogenesis, antimetastatic, and anti-inflammatory activities. In addition, GA-based synergistic approaches have been proven to enhance the healing strength of existing chemotherapeutic agents along with lesser side effects. The present review uncovers the bio-therapeutic potential of gambogic acid along with the possible mechanistic interactions of GA with its recognized cellular targets.