The present study aimed to investigate whether long-term administration of resveratrol coated with Selenium nanoparticles (RSV-Nano selenium) could shield rats from aluminum-induced AD pathogenesis and oxidative injury. Thirty male albino wistar rats were orally administered with aluminum chloride (300 mg/kg b. wt.) once daily for 30 days for induction of AD. The rats of induced model of AD were orally administrated with RSV-Nano selenium (200 mg/kg, b. wt.) once daily for 3 weeks. The rats were scarified on the 52nd and brain tissue of each rat was dissected and frozen at −80 °C. Biochemical research was conducted to determine the degree of oxidative injury through measuring Catalase, Glutathione (GSH), Malondialdehyde (MDA), γ-Secretase and Calcium levels in brain tissue. Aluminum chloride administration caused neurotoxicity and severe memory loss, as well as significant oxidative harm. It also resulted in substantial rise in γ-secretase and a significant decrease in calcium levels. RSV-Nano selenium administration increased neuronal transmission by reducing oxidative stress and metal chelation in AD model of rats (P< 0.05). In conclusion, RSV-Nano selenium protects against AD and oxidative harm caused by aluminum.