The current work was undertaken to evaluate in vitro the antimicrobial activity of two edible Mushrooms (Basidiomycetes & macrofungus), Pleurotus osteratus and Agaricus bisporus , either fresh or air dried  were assyed using aqueous and organic solvents extracts. The assays were done against a panel of standard pathogenic bacteria and fungi. Agar well diffusion assay showed that gram (+ve) bacteria were more sensitive to mushroom extracts than gram (-ve) bacteria especially Bacillus polymexa, Staphylococcus aureus  while in case of fungi, Aspergillus flavus & Fusarium moniliforme were strongly inhibited by either extracts of mushrooms . Aqueous extracts   of  either Fresh and dried fruiting bodies of Pleurotus ostreatus showed high antimicrobial activity than Agaricus bisporus extracts ,The minimum inhibitory concentration (MIC) for the two mushroom extracts were ranged between 20-40 µg/ml for pathogenic bacteria and 30-50 µg/ml for fungi. Thus indicated that the daily intake of mushroom can provide a natural covering isolation of antibiotic to fight against the common pathogenic organisms.