BACKGROUND: Non-alcoholic fatty liver disease is a liver condition that is increasing globally. Unfortunately, there are no successful or approved pharmacological treatments for non-alcoholic fatty liver disease. Hence, this study aimed to investigate the effect of therapeutic lifestyle changes on patients with overweight/obesity and non-alcoholic fatty liver disease. METHODS: A prospective, parallel-group, randomized controlled trial was conducted. The patients were randomized into intervention and control groups using tables with random numbers. In the control group, routine health guidance was provided for 3 months, while in the intervention group, diversified lifestyle intervention was provided. The body composition, visceral fat area, abdominal circumference, and body mass index of the control and intervention groups were compared before and after the intervention. Descriptive statistics, paired t-tests, and linear regression models were used for data analysis. RESULTS: A total of 115 participants (57 in the intervention group and 58 in the control group) completed the study. The intervention groups had significantly greater high-density lipoprotein cholesterol levels, basal metabolic rate, muscle mass, and questionnaire scores than the control groups (P <
0.05). Furthermore, the intervention participants had lower body mass index, abdominal circumference, triglyceride levels, low-density lipoprotein cholesterol levels, and fatty liver index (P <
0.05). CONCLUSIONS: Therapeutic lifestyle changes therapy for non-alcoholic fatty liver disease patients with overweight/obesity can significantly control body mass index, improve blood lipid levels, reduce fatty liver and body fat rates, improve basic metabolism, alleviate disease, and improve quality of life. More research is needed to determine the long-term impact of therapeutic lifestyle changes in high-risk groups.