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Plant metabolites that have shown activity against bacteria and/or environmental fungi represent valuable leads for the identification and development of novel drugs against clinically important human pathogenic fungi. Plants from the genus <i>Eremophila</i> were highly valued in traditional Australian Aboriginal medicinal practices, and <i>E. alternifolia</i> was the most prized among them. As antibacterial activity of extracts from <i>E. alternifolia</i> has been documented, this study addresses the question whether there is also activity against infectious fungal human pathogens. Compounds from leaf-extracts were purified and identified by 1- and 2-D NMR. These were then tested by disk diffusion and broth microdilution assays against ten clinically and environmentally relevant yeast and mould species. The most potent activity was observed with the diterpene compound, 8,19-dihydroxyserrulat-14-ene against <i>Cryptococcus gattii</i> and <i>Cryptococcus neoformans</i>, with minimum inhibition concentrations (MIC) comparable to those of Amphotericin B. This compound also exhibited activity against six <i>Candida</i> species. Combined with previous studies showing an antibacterial effect, this finding could explain a broad antimicrobial effect from <i>Eremophila</i> extracts in their traditional medicinal usage. The discovery of potent antifungal compounds from <i>Eremophila</i> extracts is a promising development in the search for desperately needed antifungal compounds particularly for <i>Cryptococcus</i> infections.