Abstract: Gut microbiota, as a significant exogenous constituent in the human body, has sophisticated reciprocal interactions with the immune system. On the one hand, the symbiosis between microbiota and human hosts relies on the build-up of immune tolerance against microbes. While on the other, the exogenous microbial signals from microbiota tightly regulate the development of gut-associated lymphoid tissues and priming of immune cells. Alterations of the immune system per se might also disrupt the construction of microbiota. Furthermore, dysfunction of the crosstalk between gut microbiota and the immune system could possibly contribute to both local and systemic diseases, including inflammatory diseases, autoimmune diseases, and cancers. Clinical studies have shed light on the therapeutic strategies exploiting microbiota, such as supplementation of probiotics and fecal microbiota transplantation in combination with conventional immunotherapy, which achieved improved outcomes in certain diseases. Hence, a thorough and comprehensive understanding of the immunological function of gut microbiota is becoming increasingly substantial and critical.