Nonalcoholic fatty liver disease (NAFLD), which is characterized by >5% deposition of triglycerides in hepatocytes, is often referred as a major risk factor for obesity, type 2 diabetes, and hypertension. We investigated the hepatoprotective effect of whole soybean embryos containing bioactive substances such as isoflavones and soyasaponins. For this study, mice were randomly allocated into four groups that were fed different diets for 10 weeks: normal diets and high-fat and high-cholesterol diets (HD), and HD with 10% or 20% soybean embryo powder (10SE-HD and 20SE-HD). Hepatic superoxide dismutase and glutathione peroxidase activity of the experimental groups increased during the period of the study (P < .05). Hepatic mRNA expressions of tumor necrosis factor α, nuclear factor (erythroid-derived 2)-like 2, and Caspase 3 were decreased when soybean embryos were increased in the mice's diets. Both of the soybean embryo-treated groups showed significantly decreased serum and liver triglyceride and total cholesterol. Adiponectin, AMP-activated protein kinase (AMPK) α, hydroxymethylglutaryl-CoA reductase, sterol regulatory element-binding protein-1c, fatty acid synthase, and apolipoprotein B mRNA expressions were decreased in the mice that were fed soybean embryos. We suggest that the regular supplementation of soybean embryos might be a useful treatment for preventing NAFLD and associated complications through upregulation of adiponectin-mediated AMPKα pathway parameters, which are implicated in antioxidant, anti-inflammatory, and lipid metabolism activities.