Background and Purpose: Post-traumatic epilepsy is the confirmed progression of unprovoked seizures after head trauma in the general population. This study was designed to control the devastating chronic consequences of post-traumatic epileptogenesis. Experimental Approach: Cerebral trauma was experimentally induced in Wistar rats to challenge the seizure susceptibility for futuristic PTE. The efficiency of Flufenamic acid, and fasudil hydrochloride, were assessed and compared with valproic acid for abnormal neurobehavioural symptoms, biomolecular levels, and apoptotic changes through histopathology. Key Results: Initial brain insult was successfully exacerbated the normal pathophysiology and neurobehavior changes in an experimental model. The lowered seizure threshold confirmed the epileptogenesis progression when a jab of Pentylenetetrazol(35mg/kg), gave the first successive seizure. Disrupted BBB permeability, neuronal infarction, and brain edema were found restored to normal after the treatment when compared to disease controls. The altered levels of neurotransmitters, mitochondrial complexes, cytoplasmic biomolecules/cytokines, different genes, and channel proteins were also restored to normal after 14-days treatments. No seizures have been observed with the test dose of Pentylenetetrazol. We analyzed the histopathological changes of hippocampus/cortex regions and found a significant decrease in the count of non-evident nucleoli, nuclear pyknosis, vascular congestion, and perineural vacuolization in treatment groups compared to injury controls. Conclusion and Implications: All the drugs greatly minimized the epileptogenesis cascade of futuristic PTE, confirms their neuroprotective capabilities. Flufenamic acid was found more effective with many potential abilities to minimize epileptogenesis compared to fasudil hydrochloride but its combination with valproic acid has much neuroprotection and efficacy.