Cardiovascular disease (CVD) is the leading cause of death worldwide, with physical inactivity being a known contributor to the global rates of CVD incidence. The gut microbiota has been associated with many diseases including CVD and other comorbidities such at type 2 diabetes and obesity. Researchers have begun to examine the gut microbiome as a predictor of early disease states by detecting disruptions, or dysbiosis, in the microbiota. Evidence is lacking to investigate the potential link between the gut microbiota, exercise, and CVD risk and development. Research supports that diets with whole food have reduced instances of CVD and associated diseases, increased abundances of beneficial gut bacteria, and altered gut-derived metabolite production. Further, exercise and lifestyle changes to increase physical activity demonstrate improved health outcomes related to CVD risk and comorbidities and gut microbial diversity. It is difficult to study an outcome such as CVD when including multiple factors; however, it is evident that exercise, lifestyle, and the gut microbiota contribute to improved health in their own ways. This review will highlight current research findings and what potential treatments of CVD may be generated by manipulation of the gut microbiota and/or exercise.