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Alzheimer’s disease is progressing neuronal degeneration disease leads to impairment of memory and cognitive ability. It is the most common cause of dementia and its increases with age. the present study was to investigate whether the Dehydroepiandrosterone (DHEA) and Melatonin or their mixture could potentially prevent aluminium-induced neurotoxicity in the cerebral cortex, hippocampus and cerebellum of the rat brain. The results showed that malondialdehyde (MDA) and total nitric oxide (TNO) showed significant (P< 0.001) increase in the mean values of Al intoxicated rats. However, the cortex and hippocampus SOD, CAT activities and GSH contents were significantly decreased in rats intoxicated with AlCl3.Additionally, choline acetyl transferase ( ChAT ) was a significant increase. The administration of Dehydroepiandrosterone (DHEA) and Melatonin corrected all these alterations and the maximum ameliorating effects were exhibited in the rats treated with the mixture of Dehydroepiandrosterone (DHEA) and Melatonin.