During the last decades the potential role of mushroom proteins in the prevention and treatment of human health have attracted the interest of the scientific community. This short review focuses on the nutritional value and mainly, the biological effects of proteins isolated from edible mushrooms. Mushrooms are rich in protein with high biological quality. They include ribosome inactivating proteins, lectins, antifungal proteins, ubiquitin-like proteins, protease inhibitors, ribonucleases, laccases, and other enzymes. The bioactive protein may display a great variety of important biological activities such as antifungal, antimicrobial, antiviral, antiproliferative, antimitogenic, immunomodulatory and hypotensive effects. Therefore, some of mushroom proteins with potent valuable properties have been isolated and their potential uses as therapeutic agents against human diseases have been studied.