Agaricus blazei Murrill (AbM) is a medical mushroom which has huge potential commercial value with various health-promoting functions. However, the chemical composition and therapeutic mechanisms of AbM have not been concluded systematically yet. Thus, this study aims to comprehensively summarize the phytochemical profiles and thoroughly characterize the health promotion effects such as the antitumor and antidiabetic impact of AbM in in vivo and in vitro. The AbM consists of abundant bioactive substances; polysaccharides, lipids including ergosterol, sterols, proteins, vitamin B, C and D, and phenolic compounds. Several studies have claimed that Agaricus blazei Murrill polysaccharides (AbMP) had immunoregulation, anti-inflammatory, hepatoprotective, and antitumor function both in vivo and in vitro. Meanwhile, AbM extracts were thought to cure diabetes and bacterial infection, exhibiting anticarcinogenic and antimutagenic functions. But some principles behind health-promoting effects have not been clarified. Additionally, AbM related clinical trials are limited and further discovery need to be conducted. Therefore, this paper has concluded the health promotion impact with corresponding mechanisms of AbM and indicated its potential medical usage as functional food in the future.