Typha domingensis Pers. is an aquatic Typhaceae family member. GC/MS examination of saponifiable matter of Typha domingensis Pers. aerial parts identified twenty-three known fatty acids, including 9,12-Octadecadienoic acid, methyl ester, (E, E), and 9-Octadecenoic acid (Z)-, methyl ester as the major constituents, representing peak area percentage of 11.623 % and 9.502 %, respectively. The examined plant methanol extract revealed a high total phenolic (158.3939 ± 1.867 µg gallic acid/1mg extract) and flavonoid (40.5813 ± 0.4098 µg rutin /1mg extract) contents. In this study we investigated the antibacterial activity of T. domingensis Pers. total methanol extract of aerial parts (TDME) and its successive fractions. Values of MIC were detected against several strains of bacteria. It has been found that TDME demonstrated inhibitory effects against Gram-positive bacteria (Bacillus subtilis) with MIC value 4 µ/mL equal to MIC value of the control (ampicillin). Among the tested fractions, the ethyl acetate fraction (TDEF) showed notable antibacterial activity against both Pseudomonas aeruginosa and Staphylococcus aureus bacteria with MIC values equal to that of the control. Furthermore, TDEF showed MIC value against B. subtilis lower than the MIC value of the control. The antifungal efficacy of the extracts was also investigated against Candida albicans and Aspergillus flavus compared to positive control (Clotrimazole). All the tested fractions had modest antifungal effect.