Purpose <p>This study investigated the effects of circuit resistance training (CRT) on Meteorin-like protein (METRNL), interleukin-4 (IL-4), interleukin-13 (IL-13), and metabolic health markers in overweight individuals.</p> Methods <p>Thirty overweight male university students (BMI: 25–30&#xa0;kg/m²) were randomly assigned to a 6-week CRT intervention group (<i>n</i> = 15) and a control group (<i>n</i> = 15). The CRT program comprised three weekly 45&#xa0;min sessions at 60–70% of one-repetition maximum. Serum METRNL, IL-4, IL-13, insulin resistance index, body composition, and lipid profile were measured pre- and post-interventions.</p> Results <p>The CRT group showed significant improvements compared to&#xa0;the controls. Body mass index and body fat percentage decreased, while serum METRNL, IL-4, and IL-13 levels increased significantly (<i>p</i> &lt; 0.05). Metabolic health markers improved, with reductions in fasting blood glucose, fasting insulin, HOMA-IR, total cholesterol, triglycerides, and LDL-C, and increased HDL-C (<i>p</i> &lt; 0.05). Lean body mass remained unchanged between groups.</p> Conclusions <p>CRT effectively increases METRNL secretion and its corresponding anti-inflammatory cytokines, IL-4 and IL-13, potentially contributing to overweight individuals’ improved immune and metabolic functions. This suggests its potential as a therapeutic strategy for managing obesity-related immunometabolic disorders.</p>