Apple peel extracts and their fractions pooled according to their molecular size were prepared and evaluated for their inhibitory activity against Helicobacter pylori and Jack bean ureases. Urease Inhibitory effect of apple peel polyphenols (APPE) extracted from the Granny Smith variety was concentration-dependent and reversible. High molecular weight polyphenols (HMW) were more active against Helicobacter pylori and Jack bean ureases than low molecular weight polyphenols with IC50 values of 119 and 800 microg GAE/mL, respectively. The results suggest that monomeric compounds (mainly flavan-3-ols-and quercetin-O-glycosides) will not be implicated in the antiurease effect displayed by the apple peel polyphenolic extract. Thus, as a byproduct, apple peel is suitable for developing functional ingredients that could be useful for neutralizing an important Helicobacter pylori colonization factor.