Activity-guided fractionation of the leaves of Aloe arborescens led to the isolation and characterization of the known compounds elgonica-dimers A (1) and B (2) as potent inhibitors of cytosolic alcohol dehydrogenase (c-ADH) and aldehyde dehydrogenase (ALDH) activities in vitro. Previous studies showed that the MeOH-soluble fraction of A. arborescens decreased alcohol dehydrogenase activity in rat-liver cytosol, and three active principles (aloe-emodin, aloenin, and ethylidene-aloenin) were isolated from the EtOAc-soluble extract. In the present study, compounds 1 and 2 were isolated from the n-BuOH-soluble extract and identified by comparison of their physical and spectroscopic data (UV, negative ion FABMS, 1H NMR) with literature values, which are composed of anthrone emodin-10′-C-β-D-glucopyranoside and anthraquinone aloe-emodin moieties and differ only in the stereochemical disposition at the C-10′ quaternary carbon center. Compounds 1 and 2 exhibited exceptionally high inhibitory potencies against c-ADH with IC50 values of 0.055 and 0.011 µM, respectively, which were approximately 180 and 900 times greater than pyrazole (a positive control). They also showed potent inhibitory activities against cytosolic ALDH (c-ALDH) and mitochondrial ALDH (m-ALDH). The results indicate that elgonica-dimers A (1) and B (2) are the major active principles of A. arborescens for inhibiting alcohol-metabolizing enzyme systems, and they might possess broad enzyme inhibitory activity. In vivo evaluation remains to be carried out.