The probiotic Akkermansia muciniphila ( A. muciniphila) is an intestinal bacterium that was first identified in human feces in 2004. Its specialization in mucin degradation makes it a key microorganism that maintains intestinal mucosal barrier function. As an unique representative strain of the phylum Verrucomicrobia that can be cultured in vitro, A. muciniphila is much easier to detect by metagenomic analysis of intestinal flora. In the past few years, A. muciniphila has been getting increasing attention for the positive correlation between its intestinal colonization and host homeostatic metabolism. In this review, we summarize the relationship between A. muciniphila and host health and diseases, especially focusing on metabolic diseases and related mechanisms, as well as the natural food and drug-derived substrates affecting its colonization in the host, expecting to provide evidence and clues for the development of drugs targeting A. muciniphila.