THE ANTIFUNGAL activities of six selected desert plants belonging to families Chenopodiaceae, Solanaceae, Brassicaceae, Fabiaceae, Zygophyllaceae and Aizoaceae from the North Western Mediterranean coastal region, Egypt, were investigated against six human pathogenic fungal species (Candida albicans, Candida tropicalis, Trichosporon sp., Aspergillus fumigatus, Aspergillus flavus and Aspergillus versicolor). Aqueous as well as organic crude extracts of the selected desert plants were screened against the different human pathogenic fungal species. Results demonstrate that the non-polar fraction of Atriplex halimus L. and Mesembryanthemum crystallinum L. exhibited the most antagonistic activity. The MIC values of fractions against yeasts and moulds ranged from 0.195 to 6.25mg/ml, whereas the fungicidal activity ranged from 0.781–12.5mg/ml. The most efficient antifungal activity was displayed by the petroleum ether fraction of M. crystallinum L. which inhibited the growth of yeast at MIC value of 0.195mg/ml and moulds at MIC values that ranged from 1.56–3.12mg/ml. Notably, the majority of combinations between plant extracts and antifungal drugs and/or plant extracts showed synergistic antifungal activities against the tested fungal species. As for the probable mechanism for the observed antifungal activity of the petroleum ether fraction of M. crystallinum, a considerable reduction in the ergosterol content and leakage of plasma and cellular membranes of the tested fungal species.