Background and Objective Co-morbidity of obesity, sleep disturbance, and depression is common, especially among women. We aimed to evaluate the effects of melatonin on body weight, depression symptoms and sleep among women with co-morbidities of obesity, mild and moderate depression, and sleep disturbances seeking weight reduction compared with the placebo.Methods This double-blind, randomized clinical trial was performed on 43 patients with comorbidity of mild and moderate depression, overweight/obesity (body mass index ≥ 25) and sleep disturbance. After obtaining the informed consent forms they were randomly assigned to receive 3 mg melatonin or placebo at bed-time. We performed body composition assessments, Beck Depression Inventory, Spielberger State-Trait Anxiety Inventory and Pittsburgh Sleep Quality Index at the baseline, and 2, 4, 8, and 12 weeks after initiating of the study. We analyzed the data using analysis of variance repeated measures.Results Melatonin significantly reduced depression symptoms compared with the placebo, F = (1, 34) = 6.2, p = 0.017. Also, melatonin significantly improved sleep quality, F = (1, 33) = 8.0, p = 0.008. Besides, subjects on the melatonin reduced more weight compared with the placebo but difference between groups was not significant, F = (1, 41) = 0.2, p = 0.650. Patients in the melatonin group did not show significantly more side effects compared to placebo.Conclusions Based on our findings, melatonin was not able to significantly reduce the body weight more than placebo, but as a safe over-the-counter supplement, it may be helpful in patients with co-morbidities of sleep disturbance, mild and moderate depression, and obesity in reducing the symptoms of depression and insomnia.