Introduction Triclofos and melatonin are commonly used oral sedatives in children for obtaining a sleep electroencephalogram (EEG) record. There has been no systematic review till now to compare the efficacy and safety of these two medications. Objectives The review intended to compare the efficacy of oral triclofos and melatonin in children <18 years of age for inducing adequate sedation for obtaining a sleep EEG record. We also attempted to compare the adverse effects, impact on EEG record, the yield of epileptiform abnormalities, and sleep onset latency in both groups. Methods A systematic search was conducted on MEDLINE/PUBMED, Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, Web of Science, and Google Scholar till November 30, 2020, with the following keywords/the Medical Subject Headings (MESH) terms while searching: sleep EEG, electroencephalogram, triclofos, melatonin OR ramelteon AND epilepsy, seizure, OR convulsion. ROB 2.0 and ROBINS-I tool was used to determine the risk of bias. To assess heterogeneity in studies, Higgins and Thompson's I2 method was utilized. When I2 was more than 50%, a random effects model was utilized and a fixed-effect model was used for other parameters. To assess the presence of publication bias, Egger's test was used. Results For describing the efficacy of triclofos in 1,284 and melatonin in 1,532 children, we selected 16 articles. The indirect comparison between the pooled estimate of all children receiving individual medications revealed comparable efficacy in obtaining successful sleep EEG record with a single dose (90 vs. 76%, p =0.058) and repeat dose ( p =0.054), detection of epileptiform abnormalities ( p =0.06), and sleep onset latency ( p =0.06), but more proportion of children receiving triclofos had adverse effects ( p =0.001) and duration of sleep was also higher with triclofos ( p =0.001). Conclusion Efficacy of triclofos and melatonin are comparable in inducing sleep for recording EEG in children, although triclofos is more likely to cause adverse effects. However, the level of evidence is low for this conclusion and the weak strength of recommendation for the results of this review is likely to change in the future after completion of controlled trials exploring these two medications.