Sweet basil (Ocimum basilicum L.), belonging to the family of Lamiaceae, is a spice widely used in cooking for its taste. In eastern Morocco, this plant is used as an alternative therapeutic tool to treat hyperlipidemia and prevent atherosclerosis. In this study, we aimed at the investigation of the hypocholesterolemic and hypotriglyceridemic activities of the basil methanol and aqueous fractions (MF and AF) in high-fat diet-induced hyperlipemic mice at a dose of 200 mg/kg. Hyperlipidemia was developed by a high-fat diet containing cholesterol, lard, and cholic acid during a period of four weeks. At the beginning of the experiment, animals were divided into five groups: one group served as normolipidemic control group (NCG), the second as hyperlipidemic control group (HCG), the third as methanol fraction-treated group (MFTG), the fourth as aqueous fraction-treated group and the fifth as fenofibrate-treated group (FTG). After five weeks of treatment, aqueous fraction caused a significant decrease in plasma and liver total cholesterol (−42%; P < 0.001 and −52%; P < 0.01, respectively) and triglyceride (−42%; P < 0.01 and −58%; P < 0.01, respectively). The MF reduces the plasma total cholesterol (−39%; P < 0.001) and triglycerides (−50%; P = 0.001). This fraction reduced also the liver cholesterol, but the change was not significant (P = 0.08). However, the liver TG levels were significantly reduced (−62%; P < 0.01). We noted that MF and AF significantly reduced LDL-cholesterol (−86%; P < 0.001 and −88%; P < 0.001, respectively). On the other hand, MF and AF improved the decreased profile of HDL-cholesterol (+89%; P < 0.001 and +80%; P < 0.001, respectively). Furthermore, the MF and AF showed a significant ameliorative action on elevated atherogenic index (−92%; P < 0.001 and −88%; P < 0.001, respectively) and LDL/HDL-C ratio levels (−93%; P < 0.001 and −94%; P < 0.001, respectively). This finding indicates that Ocimum basilicum may contain polar products that are able to lower plasma lipid concentrations and might be beneficial in preventing hyperlipidemia and related cardiovascular diseases.