Diabetes mellitus is a chronic condition that significantly impacts global health due to its complications and limitations in current treatments. Siddha medicine offers alternative therapies, including Athiyadhi Kashayam (AK), traditionally used for managing diabetes. This study aims to provide scientific validation for AK's antidiabetic properties. This study investigates the antidiabetic activity of Athiyadhi Kashayam (AK), a Siddha polyherbal formulation, in streptozotocin (STZ)-induced diabetic rats. Glucose levels were monitored by oral glucose tolerance test. In the diabetes-induced rats various biochemical analysis including blood glucose, lipid profile, liver and kidney function markers were also measured. The cellular changes in the tissue of liver, kidney, pancreas and heart were analysed using histopathology. From the results obtained, it is observed that AK significantly reduced blood glucose levels in diabetic rats and showed improved lipid profiles and reduced elevated levels of SGOT, SGPT, urea, and creatinine, indicating protective effects on liver and kidney functions. AK treatment preserved pancreatic islet cells and prevented liver and kidney damage. Thus, AK demonstrated significant antidiabetic activity, improving glucose tolerance, lipid profiles, and protecting vital organs in STZ-induced diabetic rats. These findings support the traditional use of AK in managing diabetes and its potential as a complementary therapy.