Background: Sarcopoterium spinosum, which is commonly named as “shrub thorny barnet”, is a well-known medicinal plant in the Mediterranean region. Traditionally, it acts as an antidiabetic agent by improving the tolerance of glucose in vivo. It is also used in inflammation and digestive disorders. Aims: This study aims to investigate the efficacy of aerial extract Sarcopoterium spinosum in protecting the liver of male Wistar rats against the induced hepatotoxic damage by the effect of carbon tetrachloride Methods: In this experimental work, 30 male Wistar rats weighing between 160-180 g were divided in to five tested groups each with 6 rats. Two groups were considered as normal control group and CCl4-intoxicated group. While the other 3 groups were treated with aqueous extract of S. spinosum with different concentration (150, 250 and 500 mg/kg body weight) by oral gavage for 21 days just before injecting the rats with hepatotoxic-carbon tetrachloride (CCl4: 3 mL/kg). Serum samples were collected from rats for assessment of certain biochemical parameters as: hepatic antioxidant enzymes (CAT, GPx and SOD), aminotransferase (AST, ALT and ALP), GSH levels, lipid peroxidation (LPO) by measuring MDA levels as well as the lipid profile (TG, LDL, VLDL and HDL). Results: This study showed that S. spinosum extract has a hepatoprotective activity by reduction of lipid peroxidation and oxidative stress as well as the aminotransferase activities in the liver resulted from exposure to CCl4. Likewise, S. spinosum seems to have a lipid lowering potential with a beneficial increase in HDL levels of the treated rats. Conclusion: Regular consumption of oral S. spinosum showed improvement in the hepatic biochemical parameters and lipid profile; which indicates that the studied extract is potent natural hepatoprotective agent. However, further studies are recommended to identify its phytochemicals that particularly exhibit these effects. © 2018, Pharmainfo Publications. All rights reserved.