The present study was undertaken to evaluate the effects of Salvia officinalis essential oil (SEO) and simvastatin in hyperlipidemic mice. Animals were randomly divided into four groups. The control group received a standard diet. The high-fat diet (HFD) group received HFD. The third and fourth groups received HFD associated either with simvastatin (2.5mg/kgbw) or with SEO (4mg/kgbw). All animals were sacrificed after 8weeks of treatment. SEO and simvastatin reduced in HFD mice body weight gain, hyperlipidemia, disruption of liver and renal functions and reactive oxygen species production. In fact, total cholesterol, triglycerides, total lipids, and low-density lipoproteincholesterol levels, as well as aspartate transaminase, alanine transaminase, gamma-glutamyltranspeptidase and lactate dehydrogenase activities were reduced, while fecal lipids increased compared to those of HFD mice. The lipid-lowering effect of SEO was more effective than that of simvastatin. PRACTICAL APPLICATIONS: High-fat diet provokes hyperlipidemia, atherosclerosis, and abnormal lipid metabolism leading to the development of hepatic and renal dysfunctions as well as perturbations of the antioxidant status in liver and kidney. The results of this research highlight the beneficial effects of SEO in the management of these disorders without inducing side effects; in fact, the plant essential oil decreased lipids and improved the antioxidant status more than did a synthetic drug.