Prolonged exposure to environmental aluminum-containing substances is associated with the development of Alzheimer's disease (AD). AD is a brain disorder associated with a gradual weakening in neurocognitive functions. Mesenchymal stem cells (MSCs) transplant as a promising and safe approach is used to treat AD through countless mechanisms. Therefore, this study aims to elucidate how MSCs improve biochemical and histopathological approaches associated with the AD model in rats. MSCs treatment restores the redox status impairment through a notable decline in the malondialdehyde (MDA) levels along with antioxidant enrichment. The anti-inflammatory effect of MSCs through conversion of microglial cells from M1 to M2 and inhibition of pro-inflammatory mediator's release work in with de-activated GSK-3β. Additionally, the alleviation of autophagy and lysosomal clearance of Aβ and tau aggregates was accompanied by a down-regulation of the mTOR. Moreover, MSCs upregulate the expression of SIRT1 together with a limited expression of miR-134 thereby, improve neurite outgrowth and synaptic loss. Overall, the obtained data confirm the novelty of MSCs in the treatment of AD not only by their antioxidant, anti-inflammatory effect but also by restoring the neural integrity, neurogenesis, improving the neurocognitive function, and modulation of the signal pathways linked to the Aβ hypothesis.