Polyphenols are widely studied phytochemicals with well-known antioxidant and anti-inflammatory properties. They are commonly present in fruits, vegetables, and plant-based foods. Beyond these classical roles, growing evidence shows that polyphenol-derived bioactive metabolites—produced or modified by the gut microbiota—can promote host health. These metabolites are increasingly recognized for shaping host–microbe interactions and influencing neurophysiological functions via the gut–brain axis. This review provides an overview of polyphenol transformation rates by the gut microbiome, highlighting their microbial transformation, anti-biofilm effects, and neuroprotective potential. In our opinion, a deeper understanding of the properties of these metabolites can significantly impact food science and biotechnology.