OBJECTIVE: The purpose of this review is to stress the complicated interactions between the microbiota and the development of heart failure. Moreover, the feasibility of modulating intestinal microbes and metabolites as novel therapeutic strategies is discussed. DATA SOURCES: This study was based on data obtained from PubMed up to March 31, 2019. Articles were selected using the following search terms: "gut microbiota," "heart failure," "trimethylamine N-oxide (TMAO)," "short-chain fatty acid (SCFA)," "bile acid," "uremic toxin," "treatment," "diet," "probiotic," "prebiotic," "antibiotic," and "fecal microbiota transplantation." RESULTS: Accumulated evidence has revealed that the composition of the gut microbiota varies obviously in people with heart failure compared to those with healthy status. Altered gut microbial communities contribute to heart failure through bacterial translocation or affecting multiple metabolic pathways, including the trimethylamine/TMAO, SCFA, bile acid, and uremic toxin pathways. Meanwhile, modulation of the gut microbiota through diet, pre/probiotics, fecal transplantation, and microbial enzyme inhibitors has become a potential therapeutic approach for many metabolic disorders. Specifically, a few studies have focused on the cardioprotective effects of probiotics on heart failure. CONCLUSIONS: The composition of the gut microbiota in people with heart failure is different from those with healthy status. A reduction in SCFA-producing bacteria in patients with heart failure might be a notable characteristic for patients with heart failure. Moreover, an increase in the microbial potential to produce TMAO and lipopolysaccharides is prominent. More researches focused on the mechanisms of microbial metabolites and the clinical application of multiple therapeutic interventions is necessarily required.