Self-assembly of amyloid beta peptide (Aβ) into the neurotoxic oligomers followed by fibrillar aggregates is a defining characteristic of Alzheimer's disease (AD). Several lines of proposed hypotheses have suggested the mechanism of AD pathology, though the exact pathophysiological mechanism is not yet elucidated. The poor understanding of AD and multitude of adverse responses reported from the current synthetic drugs are the leading cause of failure in the drug development to treat or halt the progression of AD and mandate the search for safer and more efficient alternatives. A number of natural compounds have shown the ability to prevent the formation of the toxic oligomers and disrupt the aggregates, thus attracted much attention. Referable to the abundancy and multitude of pharmacological activities of the plant active constituents, biophenols that distinguish them from the other phytochemicals as a natural weapon against the neurodegenerative disorders. This review provides a critical assessment of the current literature on in vitro and in vivo mechanistic activities of biophenols associated with the prevention and treatment of AD. We have contended the need for more comprehensive approaches to evaluate the anti-AD activity of biophenols at various pathologic levels and to assess the current evidences. Consequently, we highlighted the various problems and challenges confronting the AD research, and offer recommendations for future research.