Gymnema sylvestre (Retz.) R.Br. ex Sm., commonly known as Gurmar or Madhunashini, is an important medicinal climber with a long history of use in Indian traditional medicine. Its characteristic ability to temporarily suppress sweet taste has earned it the popular name ‘sugar destroyer.’ Traditionally, its leaves and other parts have been used for glycosuria, diabetes-related disorders, digestive and urinary ailments, inflammation, and other conditions. Modern research has linked these traditional uses with diverse bioactive constituents, particularly gymnemic acids, gymnemasaponins, gymnemosides, and gurmarin. Gymnemic acids interact with the human sweet-taste receptor complex TAS1R2/TAS1R3, providing a molecular basis for sweetness suppression. Experimental studies have further reported effects on intestinal glucose absorption, insulin secretion, glucose utilization, oxidative stress, lipid metabolism, and inflammatory pathways. Early clinical studies of standardized leaf extracts reported improvements in glycemic parameters, while subsequent randomized controlled research has provided additional evidence supporting further clinical investigation. However, clinical evidence remains limited by small sample sizes, variation in extract composition, dosage, treatment duration, and inadequate standardization. Consequently, modern applications of G. sylvestre extend beyond its traditional antidiabetic use to include functional foods, natural taste-modifying agents, standardized botanical preparations, nutraceuticals, metabolic-health research, and biotechnological production of bioactive compounds. This review examines the transition of G. sylvestre from traditional medicine to modern applications, focusing on its ethnobotany, phytochemistry, molecular mechanisms, pharmacological and clinical evidence, safety, biotechnology, conservation, and future research prospects.