BACKGROUND: Effective treatment of epilepsy is a major challenge in the field of neurology. Studies have suggested that melatonin can work in epilepsy with a good safety profile. OBJECTIVES: This study was performed to determine the effectiveness of melatonin in seizure outcomes, as well as the quality of sleep in patients with generalized epilepsy. METHODS: In this cross-over clinical trial study, 60 patients with epilepsy with idiopathic generalized tonic-clonic seizures alone (EGTCS) and under valproic acid treatment received either melatonin or placebo with a washout period of 2 weeks intermittently. Outcome variables included a reduction in the severity and frequency of epilepsy besides improvement in electroencephalogram (EEG) abnormalities and sleep quality. RESULTS: By adding melatonin, a decrease in the mean severity score of epilepsy (according to the Chalfont questionnaire) was 32.33 ± 9.24, while it was 5.58 ± 14.28 in treatment with placebo (p = .002). Evaluation of the number of attacks and EEG results did not disclose any therapeutic efficacy in treatment with melatonin versus placebo. The quality of sleep improved in 40% (first round) and 53.4% (second round) of subjects who received melatonin (p < .001). CONCLUSIONS: Considering that the addition of melatonin to routine anti-seizure treatment was effective in reducing the severity of epilepsy and improving sleep quality, it seems that melatonin can be useful as an adjunct therapy for EGTCS in well-defined circumstances.