MYCOSES and plant fungal pathogens are limiting factors highly affecting public health and crop production. Some fungal strains have been documented to be resistant to the commonly used drugs. Therefore, finding out new and pivotal antifungal drugs is becoming a global priority. Herein, we evaluated the in vitro antifungal activities of different crude polar (methanol and ethyl acetate) and non-polar (chloroform and petroleum ether) extracts of the mostly untapped brown seaweed Hormophysa cuneiformis (order Fucales, Phaeophyceae), in the Egyptian coastal waters, against eight pathogenic fungi: Aspergillus flavus, A. fumigatus, Candida albicans and Trichosporonas ahii (as human pathogens), and Alternaria alternata, Cladosporium herbarum, Fusarium oxysporum and Penicillium digitatum (as plant pathogens). The agar well diffusion assay was applied. Our findings showed that the chloroform extract only exhibited a potential antifungal activity against all tested fungal isolates, particularly T. asahii, C. albicans, A. fumigatus and C. herbarum, while the other extracts had relatively no remarkable effects. The minimum inhibitory concentrations (MICs) ranged between 0.78 and 6.25μg.ml-1 and these values are very close to those of the standard antifungal drug amphotericin B (0.63–5μg.ml-1). GC–MS analysis of the crude chloroform extract revealed 45 different bioactive compounds, mainly including 18 different species of saturated, monounsaturated and polyunsaturated fatty acids (71.48%) and some essential oils. The major constituents were arachidonic (C20:4, ω–6; 16.18%), oleic (C18:1, ω–9; 15.61%), palmitic (C16:0; 9.18%) and dihomo-γ-linolenic (C20:3, ω–6; 8.97%) fatty acids.