Ziziphus oxyphylla Edgew (Z. oxyphylla) is a small shrub to a medium sized tree. The aim of the present study was to evaluate the hepatoprotective activity of Z. oxyphylla in paracetamol-induced hepatotoxic rat model. Silymarin was used as a standard drug. Methanol extract was found to be the most potent in in-vitro antioxidant studies. The methanol extract of Z. oxyphylla was administered to experimental animals. The hepatoprotective effect of extract was evaluated by measuring liver biochemical markers, anti-oxidant enzymes and blood lipid profile. Treatment with the paracetamol increased the level of hepatic biomarkers, blood lipid profile and decreased anti-oxidant enzymes. Pre-treatment with Z. oxyphylla caused restoration of hepatic biomarkers, blood lipid profile and antioxidant enzymes levels. It is concluded that the methanol extract of Z. oxyphylla possesses hepatoprotective activity that might be due to quercetin and kaempferol glycosides present in the plant extract. Further studies are required to elucidate the exact mechanism of action of these isolated flavonoid glycosides.