This review paper is the collection of literature updates on ethnobotany, phytochemistry and pharmacological activities of a rare medicinal plant Gymnema sylvestre R. Br., (madhunashini or sugar destroyer). Gymnema sylvestre with significant medicinal properties has played an important role in Indian traditional system of folk medicine; Ayurveda and homeopathic system of medicine. Herbal preparations of Gymnema sylvestre are presently used in tea bags (herbal-chai), health tablets, supplements, beverages, confectioneries and in food items as an effective natural remedy for diabetes, asthma, obesity, arthritis, besides being used for osteoporosis, constipation and anti-inflammatory. All the herbal products of Gymnema sylvestre are available in India and international market under brand names such as HimalayaTM Pure herbs, Bangalore, India (Gymnema-sugar desroyer tablets), Vitamin Shoppe Gymnema sylvestre (sugar destroyer), Gymnema gold (Nutrigold), NovelTM Nutrients Gymnema tablets, Sandhus, diabetic tea (India) with Gymnema sylvestre, Good' N Natural (Gymnema sylvestre tablets), Product of China (Gymnema tea), Natures Plus®, The energy supplements herbal actives, Gymnema sylvestre (tablets), Natures Answer, Gymnema sylvestre (tablets), Natures way® Gymnema sylvestre (tablets), GNC® Herbal Plus Standardized, Gymnema sylvestre (tablets), Body Slatto Tea®, Gymnema®, Gymnema Diet®, Sugar Off®, GlucosetTM, Cinndrome XTM, and PilisoftTM. In India, rural community consume different parts (leaves, roots, stem and flowers) of fresly grown Gymnema sylvestre as a chief herbal medicine for the treatment of many health disorders. Therefore, herbal medicines play an important role in a primary health care sector of many developing countries. Furthermore, novel discovery of new bioactive compounds of therapeutic activities mimicking the synthetic drugs is another challenging aspect of pharmaceutical biotechnology. This also opens a new door of alternative chief herbal medicine (bioactive compounds) for many deadly viral, bacterial, and fungal diseases. Finally, the experimentally tested pharmaceutical activitis of Gymnema sylvestre also provide an opportunity for further evaluation of the proposed drugs for establishing their candidature as alternative drugs for the treatment of many human health disorders.