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Introduction Diabetic patients often consume traditional medicines, available as over-the-counter products, concurrently with prescribed conventional medicines. A study of 180 marketed Ayurvedic antidiabetic formulations showed that Enicostema axillare subsp. littorale (Blume) A.Raynal (Mamajjakah) is being used frequently in several formulations by Ayurvedic industry, particularly from the Western India. The present overview covers the classical and current literature on the plant for its antidiabetic activity. Materials and methods: The classical Ayurvedic literature, the current texts of Dravyaguna Vidnyan, Ayurvedic journals as well as pharmacological literature on E. axillare have been reviewed for its Ayurvedic Dravyaguna rationale and antidiabetic activity. Results: The earliest description of the plant E. littorale has been found in Shodhal Nighantu (12th Century) with its various synonyms and its use as an antipyretic and anthelminthic drug. Medicinal properties of the plant in classical and other texts reveal that it can best be described as laghu (light), ruksha (dry), of tikta rasa (pungent taste), ushna veerya (hot potency) and katu vipak (after-effects like pungent taste). It ameliorates pitta and kapha doshas. Its main site of action is medodhatu (adipose tissue) having pramehaghna (antidiabetic) properties. The phytochemical studies show major molecules that have shown antidiabetic properties are swertiamarin, apigenin and isovitexin. Several in vitro studies have demonstrated its antioxidant and anti-inflammatory activities; while in vivo studies have shown antidiabetic, antihyperlipidemic, antihypertensive, antiobesity, nephroprotective, hepatoprotective as well as antioxidant and anti-inflammatory activities. Several clinical studies have reported safety and antidiabetic activity in diabetic as well as prediabetics patients. Besides these, the plant has also shown nephroprotective, genoprotective activities as well as insulin sensitization. Conclusions: Wide use of E. axillare in diabetes mellitus suggests a need for thorough survey of its Ayurvedic pharmaco-epidemiology and drug utilization. The emergent data would facilitate Reverse Pharmacological study of the plant in diabetic patients. There is a potential for developing a safe and validated phytopharmaceutical antidiabetic drug.