The present study evaluated the therapeutic potential of soybean nano-isoflavone extract versus bone marrow mesenchymal stem cells derived extracellular exosomes (BMSCs-EXs) in experimentally induced neurodegen- erative diseases in rats (ND). In this study, 36 albino male rats were divided into four groups: Group I (control rats); Group II (induced neurodegenerative disease in rats by intraperitoneal injection of D-galactose (120 mg/ kg/day for 2 months); Group III (ND-induced rats treated with nano-isoflavone in doses of 10 mg/kg by oral gavage for 3 months); and Group IV (ND-induced rats treated with a single dose injection of BMSCs-EXs. The effect of BMSCs-EXs was evaluated by cerebral oXidant/antioXidant biomarkers, and mRNA gene expression quantitation for cerebral tumor necrosis factor α (TNF-α), inducible nitric oXide synthase (i-NOS) and GAPDH pathway-encoding genes by real time reverse transcription polymerase chain reaction (RT-PCR) techniques. Then, histopathological examination of the cerebral cortical tissues. Our results showed that BMSC-EXs were successfully isolated and characterized. D-galactose produced a significant rise in the number of damaged neu- rons, decreased cerebral superoXide dismutase and catalase activities, increased cerebral malondialdehyde levels, downregulated the cerebral TNF-α, and i-NOS pathway-encoding genes. Furthermore, BMSC-EXs and nano- isoflavone treatments repaired damaged cerebral tissue and recovered its function greatly following induction of neurodegenerative disease. Treatment with either MSCs-EXs or nano-isoflavones led to significant improve- ment in the histological findings, reversed the degenerative effect of D-galactose, and had a favorable therapeutic utility against D- galactose-induced neurodegenerative disease