Background: Diabetes is one of the most common non-communicable global diseases. It is the fourth leading cause of death, thus posing a serious threat to human beings. The conventional drugs developed along the principles of Western medicine are often limited in efficacy in diabetes management. However, significant evidences suggest that polyphenol-rich diet has the ability to protect diabetes complications. Objective: In this study we investigated the quantifying and profiling of phenols in Acalypha indica polyphenol-rich fraction (PLF) and their therapeutic potential on hepatic tissue damage in streptozotocin (STZ) induced diabetic rats. Materials and Methods: In this study,PLF was subjected the gas chromatography–mass spectrometry and High Resolution Liquid Chromatograph Mass Spectrometer HR-LC-MS and evaluate the liver biomarkers includes aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), bilirubin content, lipid profiles like low-density lipoprotein (LDL), total cholesterol (TC), triglycerides (TGs), and high-density lipoprotein (HDL), insulin and body weights in diabetic, PLF, and glibenclamide-treated diabetic and normal rats. Results: The result showed that PLF was significantly decreased the blood glucose levels, liver biomarkers such as AST, ALT, ALP, bilirubin content, lipid profiles like LDL, TC, and TGs and decreased the tissue damage in diabetic rats. Subsequently, insulin, body weight, and HDL levels were increased in diabetic rats. Subsequently, insulin, body weight, and HDL levels were increased. Conclusion: We concluded that Ai (Acalypha indica ) leaves have a rich number of polyphenolic compounds and those were may be protected from STZ-induced toxicity in liver of diabetic rats. Further research is necessary for this area to isolate bioactive polyphenolic compounds from Ai leaves and to be validated against STZ-intoxicated liver damage with assessing mechanism of action.