OBJECTIVE: High-fat diet is one of the most imperative risk factors for cardio-vascular disorders. Thymoquinone (TQ) is one of the active pharmacological components of Nigella sativa (black cumin). Salvia officinalis L. (sage) has been demonstrated to have diverse pharmacological actions. The main objective of this study was to determine the effects of sage and TQ combination on hyperglycemia, oxida-tive stress, blood pressure, and lipid profile in rats fed with a high-fat diet (HFD).MATERIALS AND METHODS: Wistar male rats were divided into five groups; normal di-et (ND) and HFD, in which rats were fed with a normal diet or HFD for 10 weeks, respectively. In HFD + sage group, animals were administered sage essential oil (0.052 ml/kg) orally along with HFD. In HFD + TQ group, rats were administered TQ (50 mg/kg) orally with HFD. In HF + sage + TQ group, animals received sage + TQ along with HFD. Blood glucose (BGL) and Fast serum in-sulin (FSI) levels, oral glucose tolerance test, blood pressure, liver function tests, plasma, and hepatic oxidative stress markers, antioxidant enzymes, and glutathione content, and lipid pro-file were measured.RESULTS: Sage and TQ combination de-creased the final body weight, weight gain, BGL, FSI, and Homeostasis Model Assessment -Insu-lin Resistance (HOMA-IR). The combination also lowered systolic and diastolic arterial pressures and liver function enzymes. The combination de-terred lipid peroxidation, advanced protein oxi-dation product, and nitric oxide amplification, as well as restoring the superoxide dismutase, cata-lase activities, and glutathione content in plasma and hepatic tissue. Sage and TQ combination re-duced the plasma total cholesterol (TC), triglycer-ide (TG), and low-density lipoprotein (LDL) levels and amplified high-density lipoprotein (HDL).CONCLUSIONS: The results of the current study verified that sage essential oil, together with TQ exhibited hypoglycemic, hypolipidem-ic, and antioxidant actions and thus could be a valuable addition to diabetes management.