Alzheimer disease (AD) is a widespread neurodegenerative condition that leads to progressive cognitive dysfunction in elderly population. Despite several attempts aimed at molecular determinants of AD, effective disease modifying treatment options are highly limited. Recently, use of natural supplements has gained considerable attention in AD research due to their cost effective and long lasting health beneficial properties. Resveratrol (RSV) is a naturally occurring polyphenolic compound found majorly in grapes. RSV has been shown to exert a plethora of medical benefits due to its anti-oxidant, anti–aging, anti-inflammatory, anti–malignant and neuroprotective properties. In particular, RSV has been shown to increase memory performance. The neuroprotective effect of RSV has strongly been linked to the depolymerization of amyloid β fibrils. However, the molecular targets of RSV remain the subject of investigation. This review was aimed to comprehend the existing knowledge on the neuroprotective effects of RSV and recent progress made on understanding the role RVS in the regulation of neural plasticity through a molecular target Sirtuin 1, a potential homeostatic regulator in AD.