Background. Liver diseases are a global health problem. Medicinal plants are being increasingly used to manage a wide variety of diseases including liver disorders. The aim of this study was to investigate the antioxidant properties and hepatoprotective activity of polyphenolic extract from the fruits ofTetrapleura tetraptera (T. tetraptera).Results. The extract ofT. tetrapterawas administered at doses of 50 mg/kg and 100 mg/kg for 07per osto rats before the induction of hepatotoxicity with of 2 ml/kg of 1:1 (v/v) carbon tetrachloride (CCl4) and olive oil through intraperitoneal route. Thein vitroantioxidant and radical scavenging properties ofT. tetrapterawere conducted by the FRAP method, the phosphomolybdate method, and the inhibition potential of DPPH, ABTS, OH, and NO radicals. The extraction yield ofT. tetrapterawas 19.35%. This extract contains polyphenols (273.48 mg CAE/g DM), flavonoids (5.2549 mg SE/g DM), and flavonols (1.615 mg SE/g DM). This extract showedin vitroantioxidant activity, an inhibitor power of various free radicals, and radical scavenging potential dose-dependent. The fifty-percent inhibitory concentration of the extract (IC50) for the studied radical varied from 28.16 to 136μg/L. In rats treated with the extract ofT. tetraptera, in a dose-dependent manner, the levels of hepatotoxicity markers such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) significantly increased while the enzyme activities of superoxide dismutase (SOD), catalase (CAT), and the level of reduced glutathione (GHS) significantly increased compared to the control group.Conclusions. The extracts from the fruit ofT. tetrapterademonstrate antioxidant activity and hepatoprotective effects.