Accumulating evidence supports a relationship between the complexity and diversity of the gut microbiota and host diseases. In addition to alterations in the gut microbial composition, the metabolic potential of gut microbiota has been identified as a contributing factor in the development of diseases. Recent technological developments of molecular and biochemical analyses enable us to detect and characterize the gut microbiota via assessment and classification of their genomes and corresponding metabolites. These advances have provided emerging data supporting the role of gut microbiota in various physiological activities including host metabolism, neurological development, energy homeostasis, and immune regulation. Although few human studies have looked into the causative associations and underlying pathophysiology of the gut microbiota and host disease, a growing body of preclinical and clinical evidence supports the theory that gut microbiota and its metabolites have the potential to be a novel therapeutic and preventative target for cardiovascular and metabolic diseases. In this review, we highlight the interplay between the gut microbiota and its metabolites, and the development and progression of hypertension, heart failure, and chronic kidney disease.