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Fatty liver contains a range of clinical symptoms, including the accumulation of fat in the liver parenchyma and it varies from a simple steatosis to non-alcoholic steatohepatitis and cirrhosis. Using natural therapies has always been a great concern for such health-related diseases. Herein, 6-gingerol, as a natural compound, was applied to treat non-alcoholic fatty liver induced in NMRI mice. The assessment included histological studies of the liver along with measurement of biochemical parameters, including insulin, glucose, adiponectin, leptin, HDL-C (high-density lipoprotein cholesterol), LDL-C (low-density lipoprotein cholesterol), VLDL-C (very low-density lipoprotein cholesterol), Aspartate transaminase (AST), Alanine aminotransferase (ALT), Alkaline phosphatase (ALP), SOD (superoxide dismutase), and catalase. The results demonstrated that treatment with 6-gingerol (800 mg/kg) modified the fatty liver indices by significantly reducing (p<0.001) the levels of triglyceride, cholesterol, LDL-C, and VLDL-C, glucose, insulin, insulin resistance, and leptin, whereas this treatment notably increased (p<0.001) the levels of liver antioxidant enzymes, HDL-c, and adiponectin. Therefore, 6-gingerol, in a dose-dependent mode, showed capability of improving non-alcoholic fatty liver and could offer a reliable remedy.