α-Glucosidase inhibitors are essential in the treatment of diabetes mellitus. Plant-derived drugs are promising sources of new compounds with glucosidase-inhibiting ability. TheGeum aleppicumJacq. andSibbaldianthe bifurca(L.) Kurtto & T.Erikss. herbs are used in many traditional medical systems to treat diabetes. In this study, metabolites of theG. aleppicumandS. bifurcaherbs in active growth, flowering, and fruiting stages were investigated using high-performance liquid chromatography with photodiode array and electrospray ionization triple quadrupole mass spectrometric detection (HPLC-PDA-ESI-tQ-MS/MS). In total, 29 compounds inG. aleppicumand 41 components inS. bifurcawere identified including carbohydrates, organic acids, benzoic and ellagic acid derivatives, ellagitannins, flavonoids, and triterpenoids. Gemin A, miquelianin, niga-ichigoside F1, and 3,4-dihydroxybenzoic acid 4-O-glucoside were the dominant compounds in theG. aleppicumherb, while guaiaverin, miquelianin, tellimagrandin II2, casuarictin, and glucose were prevailing compounds in theS. bifurcaherb. On the basis of HPLC activity-based profiling of theG. aleppicumherb extract, the most pronounced inhibition of α-glucosidase was observed for gemin A and quercetin-3-O-glucuronide. The latter compound and quercetin-3-O-arabinoside demonstrated maximal inhibition of α-glucosidase in theS. bifurcaherb extract. The obtained results confirm the prospects of using these plant compounds as possible sources of hypoglycemic nutraceuticals.