Atherosclerosis (As) is the main pathological factor of cardiovascular disease (CVD) which pathogenesis is diversified. Gut microbiota dysbiosis may contribute to dysfunction of metabolism and immune system causing metabolic disorders and inflammation, which play a role in plaque formation and rupture. Meanwhile, bacterial infection may lead to the formation and plaque development of As. In addition, gut flora dysbiosis may change cholesterol metabolism and microbiota-derived metabolites such as trimethylamine n-oxide (TMAO), bile acids (BAs) and short-chain fatty acids (SCFAs), which are correlated with the progression of As. Currently, researchers come to understand more about the treatment on As by modulating gut flora. Probiotics, prebiotics, fecal microbiota transplantation (FMT) and herbal medicine may be potential methods for the future treatment of As and benefit the patients of CVD.