N-acetylcysteine (NAC) and melatonin were reported to exert protective effects on testicular tissues. Thus, this study aimed to determine which of these is more efficient against obesity-induced testicular dysfunction in albino rats. Total 32 adult male rats (195 ± 10g) were divided into 4 groups: control, obese rats fed a high-fat diet (HFD), HFD+ NAC (150 mg/kg/d, ip) and HFD+melatonin (10 mg/kg/d, ip) group, for five weeks. Testes and epididymis were weighted. Lipid profile, pituitary-testicular hormones, tumor necrosis factor-α (TNFα), epididymal sperm parameters, testicular oxidant/antioxidant system, testicular and the epididymal histopathology, immunohistochemical localization for androgen receptors (AR) and Bax reaction were analyzed. Administration of NAC or melatonin significantly improved the lipid parameters, gonadal hormones, TNFα level, sperm count and abnormal morphology, oxidant/antioxidant system and the absolute testicular and epididymal mass with an enhancement of testicular architecture, AR expression and apoptosis as compared to that in the obese group. Additionally, as compared to the NAC group, the melanin group had significantly reduced BMI, total cholesterol, triglyceride, and TNFα and increased testosterone, sperm count, motility, superoxide-dismutase activity, mitigated histo-morphometrical changes, BAX expression, and increased testicular AR expression. Therefore, melatonin was more efficient than NAC in affording fortification against HFD-induced testicular dysfunction.