Cynara cornigera (CC), a member of the Asteraceae family, is widely distributed in northeastern Libya. The plant heads and leaves are traditionally used in folk medicine to manage conditions such as diabetes, hepatic dysfunction, and hyperlipidemia. The aim of this study is to investigate the effects of CC head alcoholic extract in hyperlipidemia rat models. Phytochemical screening was performed using qualitative methods. To evaluate the hypolipidemic activity, acute and sub-acute effects of CC extract (15.0% and 30.0%) were assessed in experimental rat models. The sub-acute effect of 15.0% CC extract was evaluated in diet-induced hypercholesterolemic rats fed a CCT diet (1.0% cholic acid, 4.0% cholesterol, and 0.5% thiouracil) for two weeks. Blood samples were collected to measure serum cholesterol, triglycerides, and liver enzymes, aspartate aminotransferase and alanine aminotransferase. Histopathological examination was also conducted. The phytochemical screening showed the presence of flavonoids, phenolic components, carbohydrates, tannins, and saponins. The administration of 15.0% CC showed a significant decrease in cholesterol and triglyceride levels in the protective and treatment groups. Moreover, the liver enzymes were significantly restored to normal levels in the protective and the treatment groups. In addition, the administration of CC 15.0% illustrated a normal structure and preserved parenchymal organization in the protective and the treatment groups compared with the hypercholesterolemia-induced diet. This study demonstrated that the edible CC heads ethanolic extract may have components that possess anti-hyperlipidemia activity. CC extract may prevent and protect the body from hyperlipidemia complications. Thus, the employment of such a herbal plant in conventional therapy programs may improve lipid profile.