<p>Despite being widely used to treat cardiovascular disease (CVD), there are still limitations of Traditional Chinese Medicine (TCM) for their widespread use due to undetermined pharmacological mechanisms. The emerging area of “pharmacomicrobiology” facilitates the pursuing of the complex interactions between TCM and gut microbiome as the gut microbiota influences TCM bioavailability and efficacy, vice versa TCM affects the microbial composition and function. Furthermore, research over the past decades has proved that gut dysbiosis and diverse microbial metabolites intimately related to the onset and progression of CVD. Herein, we summarize latest understanding of the TCM–gut–heart axis in CVD, with an emphasis on describing microbial changes and the associated mechanisms in CVD, elaborating the role of gut microbiota in metabolizing TCM, and how TCM can be used to treat CVD through affecting the gut microbiota. We further highlight the challenges and future directions that target TCM–gut–heart axis in prospects for personalized medicine in CVD, thus to present novel insights for developing new therapeutic approaches.</p> Graphic Abstract <p></p>