Population ageing is associated with a rising burden of cognitive decline, dementia and late-life affective disorders. Grape- and wine-derived (poly)phenols represent a chemically diverse group of bioactives whose biological relevance is shaped by structural complexity, the intervention matrix, host conjugation and gut microbial metabolism. Rather than acting as simple antioxidants, these compounds and their derived metabolites may influence interrelated pathways implicated in brain ageing, including neuroinflammation, endothelial function, synaptic plasticity, oxidative stress and gut-brain axis signalling. The gut microbiota is central to this framework as it converts poorly absorbed parent compounds into smaller phenolic metabolites and is modulated by (poly)phenol exposure. This review summarises the chemical and bioavailability features that determine intestinal and colonic availability, evaluates preclinical evidence concerning the neuroprotective potential of grape- and wine-derived (poly)phenols, and integrates clinical evidence from studies of cognitive ageing, mild cognitive impairment and Alzheimer's disease. Current evidence supports biological plausibility and justifies further investigation, but clinical findings remain heterogeneous. Future studies should prioritise chemically standardised preparations, metabolomic profiling, functional microbiome readouts, and integrated cognitive, vascular and inflammatory endpoints.
