Antibiotic resistance by Helicobacter pylori has reduced the eradication rates of multiple therapies. To overcome this crisis, we select safe nutraceutical derived agents of low price for investigation. The hydroalcholic extract of Vitis vinifera leaves beside the isolated compounds; quercetin-3-O-β-D-glucouronide (CPD1) beside its butyl ester (CPD2) which was isolated first time of the plant were investigated against six clarithromycin resistant isolated strains of H.pylori. Combination between the antibiotic clarithromycin and extract, CPD1 and CPD2 were also carried out. The hydroalcoholic extract, CPD1 and CPD2 showed distinctive inhibition zones of the growth of H.pylori in comparison to clarithromycin. CPD2 only showed synergistic effect on combination with clarithromycin. The mechanism of action was studied virtually against H. pylori HyPB and showed docking scores -7.26 and -6.89 Kcal for CPD1 and CPD2 respectively, which mean that both compounds affects colonization of H. pylori and in turn prevent formation of new generations of H.pylori.