The rampant multi-drug resistance among human pathogenic microorganisms has necessitated a continuous search for new and potent antimicrobial substances, especially among plants. Also, the importance of herbal plants as sources of alternative medicine is documented worldwide. In this study, antimicrobial activities of extracts of fruit bodies of Armillaria mellea against Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Bacillus cereus, Candida albicans and Candida glabrata were investigated. Antimicrobial components from the mushrooms were extracted using ethanol, methanol and water and examined by agar well diffusion method. The Minimum Inhibitory Concentration (MIC), Minimum Bactericidal Concentration (MBC) and Minimum Fungicidal Concentration (MFC) were evaluated for each extract of the mushroom. Results of Armillaria mellea, have shown promising antimicrobial activities against the tested organisms. B. cereus, S. aureus, C. albicans and C. glabrata were the most susceptible to aqueous extract of Armillaria mellea while ethanolic and methanolic extract showed different susceptible to the test organisms. The phytochemical analysis revealed the presence of varying levels of bioactive compounds. Saponins, protein and carbohydrate were detected in all the extracts while glycosides, alkaloids, flavonoids and tannins were found in some. The results obtained from this study suggest that Armillaria mellea has broad-spectrum of activity against microbial isolates used.