Pomegranate (Punica granatum) is an important source of polyphenols with assessed antioxidant properties. The aims of this study were: (i) the characterization of the monomeric phenolic variability on each isolated fruit component (endocarp, mesocarp, aril); (ii) the study on the effect of pomegranate fruit components on human thrombin amidolytic activity. Collectively, our data show that pomegranate components contain bioactive metabolites (mainly ellagic acid) and suggest a potential role for the pomegranate extract in the regulation of a number of physio-pathological processes involving thrombin (or thrombin-like proteinase).