BACKGROUND/OBJECTIVES: The proliferation of appearance-centered values on social media has driven non-obese adolescents towards increasingly extreme diets and exercise programs to achieve weight loss. Despite this, the effects of concurrent diets and exercise on musculoskeletal development during adolescence are unclear. This study examined whether prolonged endurance exercise (EX) with intermittent fasting during adolescence adversely affects musculoskeletal growth. MATERIALS/METHODS: Eight-week-old male Sprague-Dawley rats were assigned to 1 of 4 groups: sedentary (SED), intermittent fasting (IF), EX (treadmill running), or a combination of IF and EX (IFEX) (n = 6 per group). The rats were treated for 8 weeks, and the food intake and body weight were measured weekly. After 8 weeks of treatment, the muscle and fat masses were measured, and the bone mineral content and mineral density were assessed using dual-energy X-ray absorptiometry. The mitochondrial and antioxidant enzymes, thiobarbituric acid reactive substances (TBARs), and factors related to protein synthesis and hydrolysis in skeletal muscle were also analyzed. RESULTS: The IF and EX separately reduced the body weight, but the IFEX strategy also decreased skeletal muscle weight and bone mass. The protein levels associated with mitochondrial enzymes were significantly lower in the IFEX group. Moreover, elevated levels of skeletal muscle TBARs, forkhead box protein O1 phosphorylation, and the E3 ubiquitin ligases muscle atrophy F-box and muscle ring-finger protein-1 were observed. CONCLUSION: Eight weeks of IFEX treatment significantly impaired musculoskeletal development in healthy growing rats despite its intention to promote weight loss.