Background: Resistance and side effects of antiepileptic drugs (AEDs) pose a challenge in epilepsy therapy due to the limited drug bioavailability in penetrating the Blood-Brain Barrier (BBB). Nanoparticles can be one solution by encapsulating AEDs to enhance drug distribution to target cells. This study systematically assesses 1) the characteristics of nanoparticles, and 2) the potential of nanoparticle AEDs in managing seizures in experimental animal models. Methods: This systematic literature review is limited to studies published between 2013 and July 2023 in the PubMed, ScienceDirect, ProQuest, MEDLINE, and Scopus databases. Inclusion criteria encompass studies involving animal models of epilepsy, that exploring nanoparticle-based of AEDs. These studies compare the characteristics of nanoparticles and their antiepileptic efficacy with non-nanoparticle groups. Review articles, publications in non-English languages, and ongoing studies without published results are excluded. Result and Discussion: Fourteen studies met the inclusion criteria for this research. All studies utilized nanoparticles (n = 14). Lipid nanoparticles have a more compact size than any other nanoparticle, while the combination preparation method has an optimal nanoparticle formation in both lipid and polymeric nanoparticles. In animal model results indicated that nanoparticle-based drugs were beneficial in reducing seizure scores, improving seizure onset latency, and providing neuroprotective effects. Conclusion: The characteristics of nanoparticle drug delivery varied, influenced by formulation factors and preparation methods. Nanoparticle-based AEDs exhibit higher efficacy compared to conventional AEDs. All studies included present an opportunity for the development of epilepsy therapies, although future studies are needed to confirm these findings.