Alzheimer's disease is the most prevalent cause of dementia. The flavonoid quercetin has low bioavailability. Quercetin nanoparticles have been shown to have greater bioavailability. The purpose of the current investigation was to assess any potential histopathological damage caused by acrolein in the cerebral cortex. The potential effects of quercetin nanoparticles against the neurotoxicity caused by acrolein were also investigated. In the present investigation, rats were divided into six groups as follows: control group; acrolein-treated group in which rats were given acrolein (3 mg/kg) for 30 days; quercetin nanoparticles treated group in which rats were given quercetin nanoparticles (30 mg/kg) for 30 days; ameliorative group in which rats were given acrolein and quercetin nanoparticles at the same time daily for 30 days; protective group in which rats received first quercetin nanoparticles for 30 days, followed by acrolein for another 30 days; recovery group in which rats received acrolein for 30 days, and they left without any treatment for an additional 30 days. The results indicated that acrolein administration was linked to histopathological changes and significant damage in the cerebral cortex. These were visible in acute ischemia neuronal damage, which was manifested as nuclear pyknosis, neuronophagia, and focal areas of Malacia connected to gliosis. It has been resulted that the treatment of rats with quercetin nanoparticles protected and improved the cerebral cortex from the oxidative stress caused by acrolein. This result could pave the way for additional research in nanomedicine and a new line of therapeutic intervention in Alzheimer's disease using nanoparticles.