There is a strong link between gut microbiota and cardiovascular disease (CVD) risk factors such as coronary plaque formation, inflammation, platelet hyperactivity, and dyslipidemia. Several human and animal studies have reported an association between gut microbial metabolites such as trimethylamine-N-oxide (TMAO), short-chain fatty acids, phenylacetylglutamine, and bile acid metabolites with CVD. Besides the involvement of human blood platelets in hemostasis, they are also involved in the atherosclerosis process. Since the TMAO and phenylacetylglutamine of the gut microbiota are involved in platelet hyperactivity and dyslipidemia inflammation, gut microbiota has become an important research area in cardiovascular research. This chapter highlights the complex interactions between gut microbiota and platelet hyperactivity.