Gastrodin is one of the main active components of Gastrodia elata and has significant therapeutic value for various nervous system diseases. Its medicinal properties include smooth muscle relaxation, anti-necrosis, anti-aging, and anti-apoptosis effects. However, its possible effects on traumatic brain injury (TBI) are still unclear. In this study, the effects of gastroditin on TBI rats were investigated. The results proved that gastrodin had neuroprotective effect on TBI through alleviating brain deficits, decreasing brain water content, inhibiting neuronal apoptosis, and suppressing oxidative stress in brain tissues of TBI rats. Mechanically, gastrodin upregulated the expression of Nrf2 downstream proteins, suggesting the activation of Nrf2 pathway in brain tissues of TBI rats. In conclusion, gastrodin provided neuroprotection in TBI rats via Nrf2 pathway.