Temporal lobe epilepsy (TLE) is one of the most common forms of human epilepsy and is characterized by spontaneous recurrent seizures and cognitive deficits, often accompanied by hippocampal damage. Mutations in genes encoding for voltage-gated sodium channels have been shown to result in seizure disorders in humans. As a genetic model of TLE, we studied transgenic mice harboring a missense mutation of the sodium channel Scn2a (Nav1.2). In these mice, called Q54, spontaneous recurrent limbic motor seizures began at around 2 months of age and were accompanied by hippocampal sclerosis. We tested whether an enriched sensorimotor experience from birth (environmental enrichment) is effective in counteracting development of hyperexcitability and histopathologic changes in Q54 mice. We found that enriched Q54 animals displayed a dampened frequency of epileptic discharges and reduced hippocampal damage. Therefore, environmental enrichment from birth reduces spontaneous seizures and neuronal damage in the Q54 model of TLE.