The current study aimed to investigate the effect of orally administered raspberry ketone (RK) on ameliorating nonalcoholic fatty liver disease (NAFLD) induced in rats by high-fat high-fructose diet (HFFD) in comparison to calorie restriction (CR) regimen. Thirty male Wistar rats were divided into two experimental groups; one was fed normal chow diet (NCD, n = 6) for 15 weeks to serve as normal control group and the other group was fed HFFD (n = 24) for 7 weeks to induce NAFLD. After induction, rats in the HFFD group were randomly allocated into four groups (n = 6 rats each). One group continued on HFFD feeding for 8 weeks (NAFLD control group). The remaining 3 groups received NCD, calorie-restricted diet, or NCD along with RK (55 mg/kg/day, orally) for 8 weeks. Like CR, RK effectively attenuated NAFLD and ameliorated the changes attained by HFFD. RK upregulated the expression of the phosphorylated AMP-activated protein kinase (P-AMPK) and fatty acid oxidation factors; peroxisome proliferator-activated receptor alpha (PPAR-α) and carnitine palmitoyltransferase-1 (CPT-1) and downregulated lipogenic factors; sterol regulatory element-binding protein-1c (SREBP-1c) and fatty acid synthase (FAS) in the hepatic tissue. Also, RK improved lipid profile parameters, liver enzymes and both body and liver tissue weights. Altogether, these findings suggest that oral administration of RK, along with normal diet, ameliorated NAFLD in a way similar to CR. This approach could be an alternative to CR in the management of NAFLD, overcoming the poor compliance to long term CR regimen.