Preterm birth (PTB) is a global health issue and one of the most challenging problems affecting 12.9 million births worldwide. PTB is a multi-etiological disease and remains incompletely understood. The major cause of PTB is infection or inflammation and disruption of the vaginal microbiome, which affects the maternal immunologic response leading to PTB. The vaginal microbiome composition changes by a shift in the community are typically dominated by Lactobacillus during pregnancy. There are complex interactions between the maternal microbiome in pregnancy and the development of PTB, therefore, researchers have struggled to connect the maternal microbiome with the dysregulation of the maternal immune response in cases of PTB. The host microbiome affects alterations of the microorganisms with external stimuli such as disease, nutrition, immunity, and behavior. In this review, we discuss the complex association between the maternal microbiome and the risk of PTB and also focus on recent aspects of the prevention of PTB.