Blue honeysuckle is rich in polyphenols, and recently receiving attention because of its potential antioxidant and anti-inflammatory properties. Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease that develops hepatic inflammation and metabolic syndrome. The present study aims to study the effect of blue honeysuckle extract (BHE) on fat deposition and hepatic lipid peroxidation in a high-fat-diet (HFD)-induced mouse model. Mice were fed a normal diet (ND) or a HFD containing 0.5% or 1% of BHE or not for 45 d. Liver sections were stained by hematoxylin-eosin staining. Serum lipids were measured by a clinical analyzer. Insulin was examined by ELISA, and hepatic proteins were detected by Western blotting. Dietary supplementation of BHE dose-dependently suppressed HFD-induced obesity and hepatic fat deposition. Moreover, BHE improved glucose metabolism by increasing insulin sensitivity and attenuated oxidative stress potentially by up-regulating nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-mediated pathway.