In endeavor to have detailed account of nutritional, medicinal and pesticidal potentials of Tanzanian wild mushrooms, a study was conducted to assess the antiviral and protease activities of five edible species: Cantharellus platyphyllus and C. isabellinus from genus Cantharellus and Pleurotus djamour, P. sajor-caju and P. citrinopileatus from genus Pleurotus. Methanolic extracts were subjected to cytotoxicity lethality tests against Artemia salina Leach according to Meyer et al., (1982), in vivo antiviral tests using embryonated chicken eggs and protease tests using Screen to Nature methods. C. platyphyllus extracts had the highest cytotoxicity activity among Cantharellus species (LC50 = 7.846 ?g/ml) and of all tested species. P. citrinopileatus extracts had highest cytotoxicity (LC50 = 12.807 ?g/ml) among Pleurotus species. C. isabellinus and P. djamour extracts had stronger antiviral activities against both pox virus and infectious bursa disease virus. Other tested mushrooms showed moderate antiviral activities. All tested species showed non protease activities. While the Cantharellus species showed no protease inhibition property, Pleurotus species inhibited protein degradation similar to protease inhibitor. From these observations, the use of mushrooms as food and therapeutic substances particularly in HIV/AIDS infected persons is highly encouraged. It is recommended that further studies involving detailed biological activities (including antimicrobial, antioxidant and pesticidal activities) and determination of chemical compositions of Tanzanian wild edible mushrooms be done as the knowledge will contribute to the existing knowledge on these useful macro fungi.