Alzheimer's disease (AD) which is usually referred to as Alzheimer's is one of the popular reasons for dementia. Mg-Salvia Officinalis NPs has been known as an interesting compound with antioxidant, anti-inflammatory and cognitive properties. The possible therapeutic effect of Mg-Salvia Officinalis NPs was evaluated in Aluminum Chloride (ALCL3) induced AD. AD was induced by intraperitoneal injection of ALCL3 at a dose (100 mg/kg b. wt.) for 2 weeks. Fifty male rats were equally divided into 5 groups. Group I (Normal control): Rats received no drugs, Group II (ALCL3- induced AD): Rats injected with ALCL3 (100mg/kg b. wt./I. P) for two weeks, Group III (Mg-Salvia Officinalis NPs treated): After 14 days of ALCL3 injection, rats treated with Mg-Salvia Officinalis NPs (5mg/kg b. wt./day, orally) for four weeks. Group IV (Donepezil treated): Rats injected with ALCL3 as group II and treated with Donepezil (1mg/kg b. wt./day, orally) for four weeks. Group V (Mg-Salvia Officinalis NPs and Donepezil treated): Rats injected with ALCL3 and treated daily with Mg-Salvia Officinalis NPs and Donepezil for four weeks. The results revealed that ALCL3-induced AD rats causing significant alterations in Tau protein and acetylcholine levels in brain tissue in addition to marked elevation of serum ALT, AST activities, urea, creatinine concentrations and oxidative stress biomarkers. Treatment with Mg-Salvia Officinalis NPs to AD rats caused marked improvement effect in all previous parameters. Conclusively, Salvia Officinalis NPs treatment ameliorates oxidative stress induced by ALCL3 in rat's model of AD and enhances antioxidant defense system, and prevent the lipid peroxidation.