Chronic neuroinflammation associated with neurodegenerative disorders has been reported to be prevented by dietary components. Particularly, dietary (poly)phenols have been identified as having anti-inflammatory and neuroprotective actions, and their ingestion is considered a major preventive factor for such disorders. To assess the relation between (poly)phenol classes and their bioactivity, we used five different raspberry genotypes, which were markedly different in their (poly)phenol profiles within a similar matrix. In addition, gastro-intestinal bio-accessible fractions were produced, which simulate the (poly)phenol metabolites that may be absorbed after digestion, and evaluated for anti-inflammatory potential using LPS-stimulated microglia. Interestingly, the fraction from genotype 2J19 enriched in ellagitannins, their degradation products and ellagic acid, attenuated pro-inflammatory markers and mediators CD40, NO, TNF-α, and intracellular superoxide via NF-κB, MAPK and NFAT pathways. Importantly, it also increased the release of the anti-inflammatory cytokine IL-10. These effects contrasted with fractions richer in anthocyanins, suggesting that ellagitannins and its derivatives are major anti-inflammatory (poly)phenols and promising compounds to alleviate neuroinflammation