Hypercholesterolemia represents the most essential dangerous factor for cardiovascular diseases, which continue to be a widespread problem worldwide. The current study aimed to evaluate the therapeutic effects of costus (Saussurea lappa) in hypercholesterolemic rats. Five groups (n=7) of male albino rats (Rattus norvegicus) were randomly allotted as follows: the control group, coconut oil group (coconut oil for 4 weeks + water for other 4 weeks), cholesterol group (450 mg cholesterol powder/kg body weight dissolved in coconut oil for 4 weeks + water for other 4 weeks), costus group (water for 4 weeks + 50 mg costus roots powder/kg body weight suspended in water for other 4 weeks), the cholesterol+costus group (cholesterol for 4 weeks + costus for other 4 weeks). All treatments were given in 0.5 mL by gavage. The hypercholesterolemic rats showed marked dyslipidemia and significant increases in the serum levels of the atherogenic index, malondialdehyde, nitric oxide, and vascular endothelium growth factor, as well as the activities of serum alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase, in comparison with the other groups. Additionally, hypercholesterolemic rats had significant decreases in the serum high-density lipoprotein cholesterol level and the activities of serum superoxide dismutase and catalase, and impairment in the kidney functions, in comparison with the other groups. Costus administration modulated significantly all the changes in the serum of the hypercholesterolemic rats. In conclusion, dietary supplementation of costus has a potential/effective role in alleviating the biochemical disturbances resulting from hypercholesterolemia.