Although the mechanisms underlining the onset and development of Kawasaki disease (KD) remain to be underdetermined, the disease appears to be a result of multiple interactions between genetic and environmental susceptibility factors with an infectious trigger, followed by abnormal immune responses characterized by increased inflammatory cytokines in acute phase. The gut microbiota, a microbial community includes more than 1000 different interacting bacterial species in major and some other eukaryotic fungi, viruses, and bacteriophages in the gut, and has now associated with certain diseases such as immune-related disorders, metabolic diseases, and disorders of the nervous system. Mounting evidences have demonstrated that the gut microbiota participated in host immune system maturation. Intriguingly, gastrointestinal symptoms and complications are often observed in KD patients, and antibiotic administration has linked to the development of KD by changing the gut microbiota in infants and young children. Therefore, the gut microbiota may also play some roles in KD. In this chapter, we will summarize the involvement of the gut microbiota in childhood immune diseases, cardiovascular disease, and its relationship to KD as well as how gut microbiota and their associated metabolites influence KD onset and development.