Stroke is the fourth leading cause of death and second leading cause of disability in Japan. Advances in DNA sequencing and bioinformatics have increased identification of host-microbial interactions in various systemic diseases. This review introduces the association between microbiome and stroke in human and animal models. The microbiota directly or indirectly interacts with vascular risk factors, including age, obesity, hypertension, diabetes mellitus, and hyperlipidemia. Moreover, emerging evidence suggests that the microbiome independently affects the progression of various stroke subtypes. Finally, we introduce our ongoing stroke microbiome research to perform comprehensive analyses and discover personalized therapeutic targets.