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The online version contains supplementary material available at 10.1007/s12126-020-09404-8.The ethanol/water-soluble extracts of the roots of Smilax moranensis M. Martens Galeotti, Smilacaceae, which have been appreciated since pre-Hispanic times and traditionally used to treat type 2 diabetes in Mexico, were fractionated by the application of the affinity-directed method to identify glucose-6-phosphatase and α-glucosidase inhibitors. Mass spectrometry was used to identify the inhibitor as free ligands after released from the enzy