Alzheimer’s disease (ad) is a neurological condition that worsens over time and is characterized by the buildup of amyloid (Aβ) plaques in the brain parenchyma. Neuroprotection and cholinesterase inhibition have been the two primary techniques used in the creation of medications to date. In ad, a novel sort of programmed cell death known as ferroptosis takes place along with iron buildup, lipid peroxidation, and glutathione deficiency. The objective of the current investigation was to examine the neuroprotective and anti-ferroptotic role of nanocurcumin and Donepezil against model of aluminum chloride AlCl3 and D-galactose induced ad. The experiment was performed on 70 rats divided into (G1: control, G2: NCMN, G3: Donepezil, G4: ad-model, G5: Donepezil co-treatment, G6: NCMN co-treatment and G7: NCMN+Donepezil co-treatment). Hematological parameters and biochemical investigations as oxidative stress, liver function, kidney function, iron profile and plasma fibrinogen were evaluated. Treatment with Nanocurcumin alone or in combination with Donepezil improved oxidative stress, liver functions, and kidney functions, improve iron profile and decreased plasma fibrinogen.