Abstract: Polyphenols are secondary metabolites produced by higher plants, which have potential healthy properties on human organism, mainly as antioxidants, anti-allergic, anti-inflammatory, anticancer, antihypertensive, and antimicrobial agents.In the present review the antibacterial and antifungal activities of the most active polyphenol classes are reported, highlighting, where investigated, the mechanisms of action and the structure-activity relationship.Moreover, considering that the microbial resistance has become an increasing global problem, the synergistic effect of polyphenols in combination with conventional antimicrobial agents against clinical multidrug-resistant microorganisms was discussed.