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Appreciation of the importance of <i>Akkermansia muciniphila</i> is growing, and it is becoming increasingly relevant to identify preventive and/or therapeutic solutions targeting gut–liver–brain axes for multiple diseases via <i>Akkermansia muciniphila</i>. In recent years, <i>Akkermansia muciniphila</i> and its components such as outer membrane proteins and extracellular vesicles have been known to ameliorate host metabolic health and intestinal homeostasis. However, the impacts of <i>Akkermansia muciniphila</i> on host health and disease are complex, as both potentially beneficial and adverse effects are mediated by <i>Akkermansia muciniphila</i> and its derivatives, and in some cases, these effects are dependent upon the host physiology microenvironment and the forms, genotypes, and strain sources of <i>Akkermansia muciniphila</i>. Therefore, this review aims to summarize the current knowledge of how <i>Akkermansia muciniphila</i> interacts with the host and influences host metabolic homeostasis and disease progression. Details of <i>Akkermansia muciniphila</i> will be discussed including its biological and genetic characteristics; biological functions including anti-obesity, anti-diabetes, anti-metabolic-syndrome, anti-inflammation, anti-aging, anti-neurodegenerative disease, and anti-cancer therapy functions; and strategies to elevate its abundance. Key events will be referred to in some specific disease states, and this knowledge should facilitate the identification of <i>Akkermansia muciniphila</i>-based probiotic therapy targeting multiple diseases via gut–liver–brain axes.