Introduction: Epilepsy is a common neurological disorder; seizures and hyperexcitability are its defining features in the central nervous system (CNS). The condition known as status epilepticus (SE) can be fatal, as it involves seizures occurring. Epilepsy is typically treated with antiepileptic drugs (AEDs) like carbamazepine (CBZ). The present study aimed to establish a rat model of SE-like disease using the LiCl-pilocarpine and then utilize these rat models to evaluate the therapeutic potential of AST and/or CBZ in a solution form or loaded on NLCs via intranasal administration. Additionally, to investigate the potential molecular targets of AST and AST + CBZ-nanoformulations.Methods: After the treatment was completed, the rats underwent behavioral tests, including the rotarod and Morris Water Maze (MWM). They are then sacrificed and their brains were dissected to obtain the cerebral cortex and hippocampus for the assessment of neurotransmitters such as gamma-aminobutyric acid (GABA), serotonin, and dopamine; gene expression of GABA type A (GABAA) receptors subunits and gephyrin; indicators of inflammation like nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and High-Mobility Group Box 1 (HMGB1); antioxidant markers, including nuclear factor transcription factor E2-related factor 2 (Nrf2) and hem oxygenase-1 (HO-1).Results: The rats treated with the combination of AST and CBZ in nano-formulations seeing the best results.Discussion: Astaxanthin (AST) may reduce epilepsy-induced oxidative stress and neuronal cell death in the brain. Nano lipid carriers (NLCs) serve as better drug delivery carriers for lipophilic drugs such as CBZ and AST. AST exhibited potential anti-epileptic effects on its own, particularly as NLC-nanoformulations and when combined with conventional AEDs (CBZ).