Objective: Studying the antioxidant properties of Stevia Rebaudiana Bertoni extract as a prevention therapy on valproic acid (VPA)-induced autism rat model. Methods: Control group: female rats were injected saline 0.9% IP at GD (12.5). VPA group: female rats received single IP injection of valproic acid at a dose of 500 mg/kg at GD (12.5). Stevia control group: female rats received Stevia R. extract at a dose of 200 mg/kg orally once daily for 3 weeks, through whole gestation. Stevia prevention group: Female rats received Stevia R. extract as stevia control group and single IP injection of valproic acid at a dose of 500 mg/kg at GD (12.5). Risperidone: Female rats received single IP injection of valproic acid at a dose of 500 mg/kg at GD (12.5) and male pups received risperidone (1 mg/kg; orally) from post-natal day 23 to 43. We conducted behavioral assessments and histopathological inspection with a biochemical analysis to measure oxidative stress markers MDA and GSH levels in the hippocampal tissue. We also conducted an immunohistochemical analysis to evaluate the nuclear expression of Nrf2. Results: Stevia R. extract as a preventive therapy improved anxiety and stress associated with autism. Stevia R. decreased neuronal dystrophy and MDA level compared to VPA group. Also, increased GSH levels and increased nuclear Nrf2 expression. Conclusions: Stevia R. extract as a preventive therapy have a possible neuroprotective effect on VPA-induced autism rat model through the Nrf2-Keap1 pathway.