Incidence of tuberculosis infections is on the rise. The cost and length of orthodox treatment regimen coupled with the rise in multidrug resistance cases make the development of more effective and relatively cheaper alternative therapies imperative. The cold percolation method was used with dichloromethane as an extraction solvent to obtain dichloromethane extract of the edible mushroom Pleurotus tuber-regium. The extract was soluble in n-hexane and labeled PTHS. Antituberculosis screening was by using the colorimetric BACTEC MGIT 960 SIRES method. Phyto-constituents determination was by using standard phytochemical test reagents.The PTHS of Pleurotus tuber-regium inhibited the growth of clinical isolates of Mycobacterium tuberculosis at the test concentration of 32.5 μg/ml. Terpenoids and steroids were detected as the phytochemical constituents. This study confirmed the nutraceutical benefits of some edible mushrooms.