Antibiotic resistance has become a global concern and is threatening the clinical efficacy of many existing drugs. This has led to an increased screening of several medicinal sources of potential antimicrobial substances. Mushrooms have long been recognized as valuable source of nutritive and pharmacologically active compounds. The objectives of this study were to isolate and characterize antimicrobial compounds from selected mushroom extracts. Twelve crude extracts of mushrooms using acetone, methanol, ethanol and cold water, namely; Amanita spp, Amanita zambiana, Cantharellus heinemannianus, Cantharellus miomboensis, Cantharellus symoensii, Ganoderma lucidum and Lactarius kabansus, were separated by Preparative Liquid Chromatography (PLC). The separated bands were each scrapped off the silica plates and extracted with 15 ml ethyl acetate, filtered through Whatman no 1 paper and dried under a stream of air. The dried extracts were re-suspended in 1-10 mg/ml methanol or dimethyl sulfoxide. A total of ninety nine compounds were obtained and labelled as compounds 1 to 99. The isolated compounds were screened for their antimicrobial activity against Salmonella typhi using the tetrazolium salt (MTT) cell viability assay. Fourteen of the isolated compounds exhibited high growth inhibition of S. typhi ranging from 62-84.3%. The acetone extract of C. symoensii had the compound with the highest inhibitory activity of 84.3%, at a concentration of 480 µg/ml, followed by C. symoensii from ethanol and methanol extracts, C. miomboensis from ethanol extract and C. symoensii from ethanol extract, showing inhibitory activities of 82.8%, 82.4%, 76.8% and 76.8%, at concentrations of 800 µg/ml, 640 µg/ml, 800 µg/ml and 640 µg/ml, respectively. The tested compounds were identified using standard staining procedures with Dragendorff's reagent for the detection of alkaloids, vanillin-sulphuric acid for terpenoid and phenol derivatives, anisaldehyde-sulphuric acid for flavonoid derivatives, anisidine phthalate for carbohydrates and reducing sugars, diphenylamine for glycosides and glycolipids, ninhydrin for amines and amino sugars, phosphoric acid for sterols and steroids, and iodine for universal stain. The majority of the compounds showed a white fluorescence under UV at 254 nm. Two compounds additionally gave a purple colour when viewed under UV at 365 nm. Four compounds from methanol and ethanol extracts of C. miomboensis and acetone extract of C. symoensii, showed purple spots after staining with anisaldehyde-sulphuriric acid, indicating the presence of flavonoid derivatives. Two of the compounds further gave positive results after staining with vanillin-sulphuric acid on the same spots, confirming the presence of phenol derivatives. The results showed that Cantharellus species possessed antibacterial activity against S. typhi due to the presence of flavonoids. Appropriate extracts of Cantharellus species have potential for developing therapeutic agents against S. typhi.