The IKK 16 DPP-IV binding site is highly druggable in the sense that tight, specific binding to the enzyme can be achieved with small molecules with drug-like physicochemical properties. The two key binding-site areas for the intermolecular interaction of DPP-IV and ICI 89406 reversible inhibitors of non-peptide nature are the lipophilic S1 pocket and the negatively charged Glu205/206 pair. We have recently used coordinates from complexes between DPP-IV and potent reversible inhibitors of non-peptide nature to derive a structure-based common pharmacophore that defines a common background for DPP-IV inhibition. This pharmacophore is part of a virtual screening workflow that also includes protein-ligand docking studies and shape and electrostatic- potential comparisons. We have applied this VS workflow to the 89,425 molecules present in the natural products subset of the ZINC database, and we found that 446 of these molecules would inhibit DPP-IV with good ADMET properties. Notably, when these 446 molecules were merged with 2,342 known DPP-IV inhibitors, and the resulting set was classified into 50 clusters according to chemical similarity, there were 12 clusters that contained only natural products for which no DPP-IV inhibitory activity has been previously reported. Nine molecules from 7 of these 12 clusters were then selected for in vitro activity testing, and 7 out of the 9 molecules were shown to inhibit DPP-IV. The goal of the present work was to identify natural extracts with known antidiabetic activity that contain at least one molecule that we predict to be a DPP-IV inhibitor through a slightly modified version of the VS workflow described above. Therefore, in this study, we provide new information about the active molecules in some natural extracts with antidiabetic properties and suggest that, at least in part, the mode of action of these molecules involves stimulating insulin secretion through the inhibition of DPP-IV. We also provide a list of plants with no previously described antidiabetic activity that may contain DPPIV inhibitors and that are related to plants with known antidiabetic activity. These plants represent a new source of potential antidiabetic extracts. In addition, the new DPP-IV inhibitors that we identified are chemically different from known DPP-IV inhibitors, and therefore, they could be used as leadhopping candidates for the development of new antidiabetic drugs. Only 332 out of these 10,883 molecules have docked conformations that without reorientation, are able to match the pharmacophore. This reduction is useful because it discards those molecules that are predicted to bind in a non-productive way to the DPP-IV binding site. Finally, the later filter aims to smooth differences in chemical structures and translate them into criteria important for their intermolecular interactions with the ligand-binding site. This filter has been reported to be a valuable VS tool for the discovery of novel scaffolds, and in our case, it was applied to rescore the 332 hits that survived the previous filter.