Objective: This study aimed to evaluate the effects of eight weeks of aerobic exercise and spirulina supplementation on liver enzymes, body composition, and cardiorespiratory fitness in overweight and obese women. Methods: A randomized, double-blind, placebo-controlled trial was conducted involving 36 overweight and obese adult women (body mass index [BMI] ≥ 25 kg/m2, aged 25–40 years) randomly assigned to four groups: placebo with aerobic exercise, spirulina with aerobic exercise, spirulina-only, and placebo-only. Interventions included aerobic training three times per week (40–50 minutes/session) and a twice-daily dose (each 500 mg) of Spirulina or placebo for eight weeks. Outcomes were assessed at baseline and post-intervention, including liver enzyme levels (alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP), body composition (BMI, body fat percentage, waist-to-hip ratio (WHR)), and VO2max using validated protocols. Results: Significant within-group improvements in ALT, AST, body weight, BMI, WHR, and VO2max were observed in the aerobic training and spirulina groups, either alone or combined (p < .001). The aerobic training + placebo group demonstrated the greatest reduction in body weight and BMI, while spirulina-alone showed significant ALT and AST reductions. VO2max improved in all intervention groups, but post hoc analysis revealed no significant between-group differences. Conclusion: Aerobic exercise and spirulina supplementation independently and synergistically improve liver function, body composition, and cardiorespiratory fitness in overweight and obese women. Combining these interventions may offer a holistic approach to managing obesity-related health risks. Further research is essential to elucidate the underlying mechanisms and optimize intervention strategies for diverse populations.