Abstract: The dietary polyphenolic compounds resveratrol and quercetin prevent neurodegenerative diseases in experimental models; however, they reach the brain only in nanomolar concentrations in the glucuronidated and sulfated forms, and not as the aglycone parent form (Pasinetti et al., 2015). Recently, we found that these polyphenol aglycones and glucuronide metabolites bind with high affinity to two sites present within the peptide G region of 67-kDa laminin receptor (67LR): the “A” site, which is supported by the more hydrophobic palindromic sequence in peptide G and the “B” site, which is supported by the less hydrophobic N-terminal half of peptide G (Gopalakrishna et al., 2023, 2024). The glycosaminoglycan (GAG)-binding motif present in peptide G recognizes both the glucuronic acid moiety of glucuronide metabolites of polyphenols and the gallic acid moiety of (–)-epigallocatechin-3-gallate (EGCG) in A and B sites (Figure 1). These glucuronidated metabolites protect neuronal cells from cell death more effectively than the aglycone parent polyphenols (Gopalakrishna et al., 2023). Some dietary polyphenols may have common targets and mechanisms of neuroprotective action and may produce additive/synergistic interactions. This information may help optimize the prevention of neurodegenerative diseases with a rational combination of low doses of polyphenols for safer dietary supplementation in humans.