Nonalcoholic fatty liver disease (NAFLD) is a prevalent global health issue, characterized by hepatic steatosis and associated with metabolic comorbidities such as obesity, diabetes, and dyslipidemia. Berberine (BBR), an isoquinoline alkaloid, has emerged as a potential therapeutic agent for NAFLD. In this research, we evaluated the effects of BBR on NAFLD management and its associated complications. Our analysis included three groups involving 10 rabbits induced NAFLD by administration cholesterol rich diet, 10 rabbits administrated high rich diet with fats and cholesterol, and 10 rabbits with normal fed as control group. BBR demonstrated significant improvements in liver function biochemical markers (ALT, AST, GGT), lipid indices (TC, TG, LDL-C, HDL-C), and physiological parameters such as insulin sensitivity (HOMA-IR) and body mass index (BMI). Importantly, BBR exhibited a favorable safety profile, with minimal gastrointestinal adverse events reported. These findings highlight BBR potential as an adjunct therapy for NAFLD. However, further well-designed clinical trials involving human subjects are warranted to validate its efficacy and safety.