Low medication adherence remains a major challenge in the treatment of epilepsy, particularly in children. In recent years, several approaches and interventions have been employed to promote medication adherence in children with epilepsy (CWE). In this study, we aimed to summarize the evidence on these interventions. In this systematic review, major medical electronic databases were searched for relevant literature from January 2005 till July 2023, including PsycINFO, Medline (via PubMed), Google Scholar, Taylor & Francis databases, and CENTRAL by the Cochrane Library. We planned to include observational studies (with a control arm) and clinical trials involving children/adolescents (<19 years) with epilepsy and/or their caregivers/families who underwent any intervention to improve adherence to anti-seizure medications. Out of 536 articles searched, eight (six randomized trials and two non-randomized intervention studies) were included in the systematic review. A total of 2,685 children/adolescents along with their caregivers participated in these studies. Six studies used educational and two used behavioral interventions to improve adherence to anti-seizure medications. Four studies showed variable levels of adherence improvement, ranging from 2-20% up to 73.9% post-intervention. To conclude, the findings suggest the potential for educational interventions to promote medication adherence in CWE. The class of evidence was II to III among the included studies, as per American Academy of Neurology guidelines