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The oxidative stress plays a key role in Alzheimer's disease (AD) and Sirtuin (SIRT1) is potential mediator of oxidative pathway. This study explored the role of Syzygium aromaticum on SIRT1 and oxidative balance in amyloid beta induced toxicity. Anti-oxidative capacity of Syzygium aromaticum was performed in Aβ25–35 induced neurotoxicity in neuronal cells. Superoxide dismutase, Catalase and Glutathione enzyme activity were determined by the treatment of Syzygium aromaticum. Both recombinant and endogenous SIRT1 activity were performed in its presence. The expression of γ-secretase and SIRT1 were evaluated by western blot. Syzygium aromaticum was capable to scavenge ROS and elevate the percentage of anti-oxidant enzymes. It also activated and elevated the level of SIRT1 and downregulated γ-secretase level. These findings show a holistic approach towards the neurodegenerative disease management by Syzygium aromaticum which could lead to the formulation of new drug for AD.This Ayurvedic product can give a healthy aging with no side effects and also be cost effectives. It may meet unmet medical needs of current relevance.Syzygium aromaticum scavenged ROS and elevated SOD, CAT and GSH in SH-SY5Y cells.Syzygium aromaticum activated and elevated SIRT1 in Aβ25–35 induced toxicity.Syzygium aromaticum activated recombinant SIRT1.Syzygium aromaticum activated SIRT1in serum of Alzheimer's disease and MCI patients.Syzygium aromaticum downregulated γ-secretase level neurotoxic neuronal cells.