AbstractWe investigate the effect of the banana green peels extract (BPE) as a preventive treatment against NAFLD in high‐fat diet fed mice. Mice received daily doses of 100 or 250 mg/kg of BPE for 12 weeks along with the high‐fat diet. BPE reduced weight gain (p < .0001), adipose tissue hypertrophy (p < .0001), and improved glucose homeostasis (p < .0001). Plasma levels of glucose‐dependent insulinotropic polypeptide, triglycerides, total cholesterol, LDL‐cholesterol, non‐esterified fatty acids, aspartate and alanine transaminase, leptin, and resistin were decreased in BPE treated mice (p < .05). BPE effects on lipid metabolism were associated with decreased gene expression of lipogenic enzymes and increased expression of enzymes related to fatty acid and cholesterol degradation (p < .05). Plasma and liver bile acid (BA) profiles were modulated by BPE, with positive correlations between specific BA and UCP‐1, CPT‐1 and PGC‐1β expression in brown adipose tissue (p < .05). BPE reduced hepatic steatosis and inflammation, possibly due to reduced p65 NF‐κB nuclear translocation (p < .05) and modulation of oxidative stress (p < .05). These data indicate that BPE is a source of phytochemical compounds with promising effects toward the prevention of metabolic disorders associated with obesity.