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This study aimed to investigate the effects of Mentha spicata L. (Lamiaceae), which contains caffeic acid, rosmarinic acid, alpha tocopherol, and eugenol, on hormonal regulation of energy metabolism in rats. Obesity is a risk factor for various diseases such as hyperlipidemia, arteriosclerosis, and fatty degeneration in the liver. Furthermore, it has been aimed to inquire the effect of the Mentha spicata L. whether it is effective as a liver protective factor in rats fed on high fat diet. In this study, 70 Wistar-Albino male rats aged 2±3 months were used. The animals were allocated into 7 groups (10 rats in each group): 1 control group and 6 experimental groups, including negative control; carboxymethyl cellulose (CMC); high-fat diet, positive (HFD); M. spicata petroleum ether extract (PE); M. spicata ethyl acetate (EtOAc) extract; and M. spicata methanol (MeOH) extract. All experimental groups were given dietary fat and M. spicata extracts, excluding the control group. The group C rats were fed the standard rat diet; group CMC high-fat diet (40% beef tallow + 1% cholesterol) + 1 mL 0.5% CMC; group HFD high-fat diet; and groups PE, EtOAc, and MeOH petroleum ether, ethyl acetate, and methanol extracts of M. spicata, respectively, via gastric gavage for 60 days. The plasma concentrations of hormones [leptin, ghrelin, adiponectin, insulin, and thyroid hormones (T4, FT4, T3, and FT3)], glucose, aspartate aminotransferase, alanine aminotransferase, total protein, and lipid profiles (cholesterol, low-density lipoprotein, high-density lipoprotein, and triglycerides) were monitored. The histopathologic examination revealed fatty degeneration in the liver tissue and perivascular accumulation of inflammatory cells in the experimental groups. The PE extract obtained from M. spicata was effective in maintaining the body weight and protecting against liver degeneration. Further studies are required to verify this. © 2019 Parlar Scientific Publications. All rights reserved.