Background: Nonalcoholic fatty liver disease (NAFLD) is a chronic pathological condition of the liver due to excess triglyceride accumulation in hepatocytes. The antioxidant properties of curcumin improve lipid dysregulation and reduce reactive oxygen species (ROS). The aim of the study: This study explores the effects of curcumin administration on beclin-1 and microtubule-associated protein light chain-3 (LC3) expression as autophagy markers and XBP1 spliced as a marker indicating endoplasmic reticulum stress in ameliorating HFD-induced NAFLD in mice. Materials and methods: Twenty-four ddY male mice were divided into four groups: the normal chow group, high-fat diet (HFD) group, HFD with curcumin 50 mg/kg for 28 days group, and HFD with curcumin 100 mg/kg for 28 days group. Bodyweight and food intake were measured daily, and curcumin was administered intraperitoneally. The animals were sacrificed 24 hours after the last treatment. The liver was collected for macroscopic and histopathological assessment and molecular analysis using the reverse transcription-polymerase chain reaction (PCR) method. Results: Curcumin 50 and 100 mg/kg improved macroscopic and histopathological features of the liver. The results of the molecular analysis showed that curcumin 50 and 100 mg/kg did not increase the beclin-1 or LC3 mRNA expression in the liver (p>0.05). Meanwhile, curcumin 100 mg/kg significantly increases the XBP1 spliced expression in the liver (p<0.05), which indicates that curcumin modulates endoplasmic stress induced-NAFLD in a dose-dependent manner. Conclusion: Curcumin overcomes endoplasmic reticulum stress in the high-fat diet-induced NAFLD in mice.