This study was aimed to evaluate the probable protective effects of Digera muricata methanol extract (DME) against acrylamide (AA) induced hepatocellular injuries in female Sprague-Dawley rat. Phytochemical screening for the presence of different bioactive chemical groups was also carried out. The daily dose (6 mg/kg bw ip) injection of AA for 15 days caused significant increase in serum level of liver marker enzymes and metabolites: AST, ALT, ACP, ALP, LDH, BUN, creatinine, direct bilirubin and total bilirubin, while significant decrease in total protein and albumin. Hepatic level of antioxidant enzymes; CAT, POD, SOD, GSH-Px, GST and QR, and GSH contents were significantly decreased, while γ-GT and MDA was significantly increased. Treatment of DME (100, 150 and 200 mg/kg), dose dependently, ameliorated the toxicity of AA and the studied parameters were reversed towards the control level. Hepatic lesions induced with AA were reduced with DME treatment. Phytochemical screening indicates the presence of flavonoids, alkaloids, terpenoids, saponins, tannins, phlobatanin, coumarins, anthraquinones and cardiac glycosides. Total phenolic and flavonoids contents were 205±0.23 and 175.0±0.65 mg/g as equivalent to gallic acid and rutin, respectively in DME. In conclusion, the results suggest that the hepatoprotective effects of DME against AA-induced oxidative injuries could be attributed to the phenolics and flavonoids.