Current nonpharmacological approaches, including diet and exercise interventions, for preventing and treating gestational diabetes mellitus are effective for less than 50% of women. Recent evidence suggests that the gut microbiome is integrally involved in maternal glucose homeostasis. Changes to the composition and metabolic behavior of the gut microbiota may play a role in the development and persistence of gestational diabetes mellitus. Thus, there is growing interest in targeting the maternal gut microbiome for preventing and managing pregnancy-related diseases including gestational diabetes mellitus. Future progress may come from a systems biology approach to elucidate the role of the gut microbiota in maternal glucose homeostasis.