Abstarct: Background: Obesity is a major risk factor for mextabolic disorders and cardiovascular diseases and is associated with elevated circulating levels of betatrophin (ANGPTL8), insulin resistance, and impaired lipid mextabolism. Exercise training is considered one of the most effective non-pharmacological interventions for improving mextabolic health; however, the effects of different exercise intensities on betatrophin and mextabolic factors remain unclear. Therefore, the present study aimed to compare the effects of eight weeks of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on serum betatrophin levels and selected mextabolic factors in inactive obese men. Methods: This semi-experimental study employed a pretest–posttest design with a control group. Thirty inactive obese men aged 30–40 years were randomly assigned to three groups (HIIT, MICT, and control; n = 10 per group). The training intervention was performed three sessions per week for eight weeks. Blood samples were collected before and after the intervention to determine serum betatrophin, fasting blood glucose, insulin, total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). Data were analyzed using one-way analysis of variance (ANOVA), Tukey's post hoc test, and Pearson's correlation coefficient at a significance level of P < 0.05. Results: Both HIIT and MICT significantly reduced serum betatrophin, fasting insulin, fasting blood glucose, total cholesterol, LDL-C, and triglyceride levels while significantly increasing HDL-C compared with the control group (P < 0.001). HIIT was significantly more effective than MICT in reducing serum betatrophin and total cholesterol, whereas no significant differences were observed between the two training protocols for the remaining mextabolic variables. Furthermore, serum betatrophin showed significant positive correlations with total cholesterol, triglycerides, LDL-C, insulin, and fasting blood glucose, and a significant negative correlation with HDL-C. Conclusion: Both HIIT and MICT effectively improved mextabolic health and reduced serum betatrophin levels in inactive obese men. However, HIIT demonstrated greater efficacy in reducing betatrophin and total cholesterol. Therefore, high-intensity interval training may be considered a time-efficient and effective exercise strategy for improving mextabolic health and reducing obesity-related mextabolic risk.