The aim of the study was to investigate in vitro potential antioxidant and hepatoprotective effects of methanolic extracts from the aerial parts of Matricaria pubescens, Centaurea incana, and Santolina africana, against carbon tetrachloride induced liver damage in rats. The different aerial parts of three methanolic extracts, exhibited antioxidant activity in the DPPH free radical (IC50, 0.032, 0.087 and 0.044 mg/ml) respectively. The reducing ability of the extracts showed a dose-dependent trend increasing with increase in the concentrations of the extracts.The antioxidant activity of samples at the concentration of 2 mg/ml was reflected in their ability to inhibit the bleaching of β-carotene. Treated groups with extracts of studied three plants showed decrease in plasma levels of AST, ALT, ALP, and an increase in plasma catalase levels activities, while hepatic MDA decreased and catalase increased as compared to carbon tetrachloride treated groups. In consistency with in vivo and in vitro results, extracts of all three plants ameliorated the carbon tetrachloride extensive damage to liver tissue of treated animals, but, Santolina africana extract was the most efficient.