Polyphenols are produced by all higher plants in order to protect them against biotic and abiotic stress such as UV radiation, temperature changes, infections, wounding, and herbivores. When in contact with human skin, polyphenols exert either curative or damaging action depending on their physical-chemical properties, bioavailability through cutaneous barrier, metabolism in the skin, and individual sensitivity. This review will focus on 1) synthesis and metabolism of polyphenols and their role in the plant physiology, 2) non-enzymatic and enzymatic polyphenol transformation in the skin, 3) polyphenols as inhibitors or inducers of inflammatory response in the skin, and 4) photo-protective versus photo-toxic effects of polyphenols. The potential consequences of these controversial effects on the use of plant polyphenols in dermatology and cosmetology will be also discussed.