The aim of the present study was the search for the industrial exploitation potential of 15 Hypericum species crops from Portugal. Although Hypericum perforatum is well known worldwide, scarce studies have been published of Hypericum spp. identified in Portugal.Extracts from 15 Hypericum species were screened for its antimicrobial activities against 2 Gram− and 2 Gram+ bacteria, 4 non-tuberculous Mycobacterium species, a reference strain H37Rv and 4 drug-resistant strains of Mycobacterium tuberculosis, as well as 4 drug-resistant clinical isolates.In terms of Gram – standards, H. humifusum and H. elodes were the most active against Agrobacterium tumefasciens, with MIC of 2.5μg/mL. H. elodes and H. hircinum subsp. majus extracts were the most active against MDR-TB strains and isolates, with MIC of 25–100μg/mL and both exhibited significant effect against MDR-TB clinical isolates. With the exception of H. androsaemum and H. linarifolium all Hypericum species were active against Staphylococcus aureus, the H. perfoliatum and H. elodes at the level of 6 and 12μg/mL, respectively, and none showed activity on E. coli.Reference compounds isolated from H. perforatum were also tested and might contribute to the activities observed. The profile of the 15 Hypericum spp. as effective antimicrobial therapy against multidrug resistant pathogens is now available, providing scientific validation on a few available ethnopharmacological data resources.This study may be a starting point for the research on the role of various Hypericum species in integrative medicine for infection control of S. aureus and MDR-MTB. Hypericum species may also constitute a source of new leads towards the discovery of either new candidates and biologically active compounds for pharmaceutical interest, for the treatment of multidrug resistant diseases.