Alzheimer’s disease (AD) is the most common neurodegenerative disease across the world. The major cause of AD is extensive oxidative stress and inflammation in central nervous system (CNS). Vitamin D3 and E are the most known vitamins that control oxidative stress and mitochondrial respiratory function. They may prevent neuronal loss in AD. Few studies have been conducted to assess the effect of vitamins on AD. Therefore, the aim of this study was to assess the effect of vitamin D3 and E on AD. Methods: In this study, 60 rats were randomly divided into six groups (n = 10) namely the control group, sham group, AD group with intra-hippocampal Aβ1-40 injection, AD+vitamin D3 group, AD+vitamin E group and AD+vitamin D3 and E group. Memory and learning were measured by the Novel Object Recognition (NOR) test. Neuronal survival was assessed by H&E and cresyl violet staining, and oxidative stress was measured by malondialdehyde (MDA) level and superoxide dismutase (SOD) activity. In vitamin-treated groups, learning and memory, which were measured by NOR, improved significantly. Vitamin D3 and E administration decreased neuronal loss in AD brain rats. Results: Results showed that MDA decreased and SOD increased in treatment groups; but, a combination of vitamin D3 and E was more effective in decreasing oxidative stress in AD compared to other treatment groups. Conclusion: The present study indicated that vitamin D3 and E and their combination can improve memory and learning deficit, and decrease neuronal loss and oxidative stress in Alzheimer’s model.