Oxidative stress is an important part of diabetic physiopathology; therefore, naturally derived antioxidants as therapeutic agents are needed. The present work examined the antioxidant and antidiabetic potentials of seed extract of Phyllanthus acidus (L.) Skeels. Ethanolic seed extract of P. acidus (PSE) was prepared using Soxhlet extraction. Preliminary phytochemical analysis, total phenolic (TPC), and total flavonoid (TFC) contents of PSE were determined. The in vitro inhibitory effects of PSE on 1,1-diphenyl-2 picrylhydrazyl (DPPH), 2, 2-azino-bis (3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) free radicals, alpha-amylase, and a-glucosidase enzyme inhibitory activities were also assessed. Acute oral toxicity of PSE was carried out in female Sprague Dawley (SD) rats. PSE's hypoglycaemic effect was demonstrated in normoglycemic and streptozotocin-induced (STZ, 55 mg/kg, ip) diabetic rats. The TPC and TFC were found to be 3.19 mg of gallic acid equivalent/g (GAE/g), and 2.58 mg of quercetin equivalent/g of extract (QE/g), respectively. The inhibitory concentration 50% (IC50) values, based on the inhibition of DPPH (IC50 28.26 +/- 0.39 mu g/mL), ABTS (IC50 23.44 +/- 0.48 mu g/mL) radicals, alpha-amylase (IC50 26.83 +/- 0.39 mu g/mL), and alpha-glucosidase (IC50 19.12 +/- 0.26 mu g/mL) enzymes were generally lower, which demonstrated their potent antioxidant and antidiabetic effects, respectively. Based on the acute oral toxicity test, two doses (100 and 200 mg/ kg) of PSE were tested in normoglycemic rats. A significant (p < 0.01) fall in blood glucose was observed at 8 and 12 h after PSE (200 mg/kg) treatment. The same dose was tested in STZ rats and compared with glibenclamide (5 mg/kg). A significant (p < 0.01 and p < 0.001) decrease in the blood glucose level was observed after 8 and 12 h of PSE treatment, respectively. These findings suggest that PSE could be used as an active ingredient in herbal formulations to manage diabetes mellitus. (C) All Rights Reserved