Non-alcoholic fatty liver disease (NAFLD) is a hepatic condition with multiple pathological features and it currently has no specific treatment or approved drug. Wonderful kolanut widely consumed fresh or cooked has been applied in the treatment of numerous diseases in folk medicine. In this study, we evaluate the therapeutic potentials of hydroethanolic extract of defatted Buccholzia coriacea seeds (HEBCS) in NAFLD model. HEBCS was subjected to liquid chromatography – mass spectrometry, and 30 male BALB/c mice (28 ± 2 g) were allocated to three (3) experimental groups (n = 10/group). Mice in group I were fed chow diet (CD); those in group II, high fat diet (HFD) and group III, HFD and 250 mg/kg HEBCS p.o. daily for six weeks. HEBCS alleviates HFD-induced insulin resistance and high plasma insulin and glucose levels. It further alleviates hepatic steatosis, and alters plasma lipid profile. HEBCS also protected against HFD-induced inflammation, oxidative stress and hepatocellular damage. In conclusion, HEBCS alleviated NAFLD in mice via suppression of insulin resistance, hyperlipidemia, inflammation and oxidative stress. Practical applications: Bioactive polyphenols and alkaloids were identified in hydroethanolic extract of defatted Buccholzia coriacea seeds (HEBCS). This study projects HEBCS as a potential therapeutic agent in the treatment of NAFLD. NAFLD is a multi-factorial condition and therefore, HEBCS is promising considering its multiple-target actions in the current model of NAFLD. HEBCS alleviates insulin resistance, metabolic dysfunction, steatosis, and inflammation in this model. There is a need to further investigate HEBCS in other models of NAFLD as a lead to future use in clinical studies. © 2021 Wiley Periodicals LLC.