Gut microbiome regulates host metabolism and immunity via their metabolites, secretions, and cellular components, and protects the host from pathogen invasion. Low diversity and dysfunction of the gut microbiome caused by environmental changes, unhealthy dietary habits and lifestyles, and antibiotics abuse are closely related to disease pathogenesis. Gut microbiome can serve as diagnostic and therapeutic tools for diseases related to gut microbiome dysbiosis. In this article, we aim to review the latest study advances on gut microbiome in the pathogenesis and therapeutics of gastrointestinal diseases, such as Clostridium difficile infection, Helicobacter pylori infection, inflammatory bowel disease, and irritable bowel syndrome, so as to shed light on the prospect of gut microbiome modulations in disease therapies.