This study aimed to prepare and evaluate agmatine cubosomes nose-to-brain delivery for epilepsy. Agmatine alleviates epileptic seizures and Hippocampal neuronal damage. Glyceryl-monooleate and pluronic F127 (9:1 w/w) were melted at 60°C and mixed. To prepare the cubosome dispersion, the low-viscosity homogenous melt was either added drop-wise or injected into excess water. With continuous stirring, the concentration of lipids in the sample was approximately 8–10% (w/w). The particle size and zeta potential agmatine cubosomes of F7 were found to be -270.4 nm and 12.0 mV respectively. The maximum entrapment efficiency of the agmatine-loaded cubosomes was found to be 88.92±0.33 (% w/w) for batch F7 indicating that most of agmatine was encapsulated in cubosomes. Over 12 hours, more than 95% of the agmatine released from cubosomes was released, and the drug release is 0.00 0.00, 3.80 0.54, 6.79 0.86, and 15.44 0. 39, 23.56±0.51, 26.88±0.67, 29.65±1.39, 35.78±3.66, 43.89±1.32, 52.84±1.12, 61.79±1.24, 69.38±1.32, 78.94±1.14. After nasal administration of agmatine cubosomes, onset of convulsion and duration of convulsion were found to be 611±3.3 sec and 16±5.3 sec, respectively. This result demonstrated an increased onset of convulsion and decreased convulsion duration in comparison with intraperitoneal administration of diazepam (standard).