Metabolic syndrome (MetS) is a kind of metabolic disorder, including abdominal obesity, hyperglycemia, dyslipidemia, hypertension, etc. Dietary intervention was thought to be one of the lifestyle strategies, along with others like nutritional intervention, psychological intervention, etc., that might effectively treat MetS. the ketogenic diet (KD) is a high-fat diet that has been shown to be helpful in a variety of diseases such as polycystic ovarian syndrome, acne, cancer, and respiratory distress. The study was conducted to investigate the therapeutic potential of a ketogenic diet on rat MetS models. In this study, 40 males’ rats were divided into four groups, for a period of 24 weeks, the rats were received KD. Some biochemical, molecular parameters and histopathology of liver tissues were determined. Our results demonstrated that compared to rats in the MetS group, the KD group and MetS +KD group reduced glucose, insulin, HOMA-IR, alanine aminotransferase (ALT), aspartate aminotransferase (AST), Alkaline phosphatase (ALP) levels and Malondialdehyde (MDA), while the KD group and MetS +KD group increased glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) levels (P < 0.05). An upregulation was found in the gene expression levels of the homogenate of Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and the Glucagon-like peptide-1 receptor (GLP-1R) in control group, KD group, and MetS +KD group compared with Mets group. In conclusion based on these results, KD can be suggested as a healthy weight loss diet with positive metabolic and hepatic benefits
