Epilepsy is one of the most common neurological disorders and there is a pressing need to explore therapeutics based on Complementary and Integrative system of medicines. The present study was designed to validate the protective action of a homeopathic medicine Nux vomica on mice in experimental epilepsy, and also to elucidate its probable mechanism of action. A pharmacological experiment was designed comprising four groups of mice: normal, control, Nux vomica-treated, and diazepam-treated. Subsequent transcriptome-profiling was carried out using RNA-seq to assess molecular-level changes in affected brain-tissues. Pharmacological study demonstrated that Nux vomica significantly (P < 0.05) prolonged the survival rate, survival time, and suspended the onset of convulsion. RNA-seq further furnished important insights pertaining to the mechanism of action of homeopathic medicine. Our study provides evidence-based support for the protective action of a potentized homeopathic medicine in experimental epilepsy, and also confers its modus operandi at the molecular level. Our study also points toward the fact that homeopathic medicines indeed act at the level of gene expression.