Alzheimer's disease (AD) is one of the most common neurodegenerative diseases among elderly people around the world. The main pathophysiological pathway of AD is the misfolding of amyloid-beta (Aβ) peptide into fibrillar aggregates that result in formation of neurofibrillary tangles and severe brain damages. Carica papaya has been used as traditional herbal medicine against various diseases in India and China. In this manuscript, we have explored the effectiveness of tertiary butyl methyl ether fraction from methanol extract of dried papaya leaves as a neuroprotective candidate. We have performed Thioflavin T (ThT) assay and docking studies to perceive the inhibition of Aβ-42 aggregation, a hallmark of AD. This fraction is non-cytotoxic in nature and shows neuroprotection against anti-Nerve Growth Factor (anti-NGF) induced cytotoxicity in PC12 derived neurons and confers significant stability to intracellular microtubule. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim