Objective. This study has investigated the antimicrobial activity of extracts of indigenous wild mushrooms against selected organisms. Methods. Thirty-five (35) indigenous wild mushrooms were collected from Arabuko-Sokoke and Kakamega National Reserve Forests, Kenya. All mushrooms were identified and their contents were extracted and screened for their antimicrobial activities against Escherichia coli (clinical isolate), Klebsiella pneumoniae (ATCC 13883), Pseudomonas aeruginosa (clinical isolate), Pseudomonas aeruginosa (ATCC 27853), Staphylococcus aureus (ATCC 25923), MRSA (ATCC 33591), Candida albicans (clinical isolate), and Candida parapsilosis (ATCC 90018) using tetrazolium microtiter plate bioassay method. Results. Of the 35 tested mushroom extracts, extracts of three (3) mushrooms, namely, Trametes spp. (Arabuko-Sokoke forest), Trametes, and Microporus spp. (Kakamega forest), have shown promising antimicrobial activities against the tested organisms. The S. aureus (ATCC 25923), P. aeruginosa (ATCC 27853), and Methicillin-Resistant Staphylococcus aureus (MRSA) (ATCC 33591) were the most susceptible to chloroform extract of Trametes spp. collected from Arabuko-Sokoke forest. Of the tested organisms, S. aureus (ATCC 25923) was the most susceptible whereas E. coli was the most resistant organism to the hot water extract of Trametes spp. collected from Arabuko-Sokoke forest. Chloroform extract of Microporus spp. has shown the highest antibacterial activity against S. aureus (ATCC 25923), MRSA (ATCC 33591), and K. pneumoniae (ATCC 13883) but limited activity against E.coli. All extracts of the three wild mushrooms have shown the most antibacterial activities against S. aureus (ATCC 25923). Conclusion. The present study has shown that the extracts of the three wild mushrooms have shown promising antimicrobial activities against the tested organisms.