Microbiota–host interaction has attracted more and more attentions in recent years. The association between microbiota and host health is largely attributed to its influence on host immune system. Microbial-derived antigens and metabolites play a critical role in shaping the host immune system, including regulating its development, activation, and function. However, during various diseases the microbiota–host communication is frequently found to be disordered. In particular, gut microbiota dysbiosis associated with or led to the occurrence and progression of infectious diseases, autoimmune diseases, metabolic diseases, and neurological diseases. Pathogenic microbes and their metabolites disturb the protective function of immune system, and lead to disordered immune responses that usually correlate with disease exacerbation. In the other hand, the immune system also regulates microbiota composition to keep host homeostasis. Here, we will discuss the current advances of our knowledge about the interactions between microbiota and host immune system during health and diseases.