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Abstract Mouth is the gateway to the total body wellness. Accordingly, oral microbiome influences overall health of an individual. Oral microbiome plays a key role in shaping up the host’s health profile. Obvious differences have been reported between patients with gastrointestinal diseases and healthy controls. The oral and gut microbiome profiles are well-segregated due to the oral–gut barrier. However, the oral microbiota can translocate to the intestinal mucosa in conditions of the oral–gut barrier dysfunction. Oral bacteria can disseminate to the distal gut via enteral or hematogenous routes. The translocation of oral microbes to the gut may give rise to a variety of gastrointestinal diseases including Helicobacter-induced diseases, irritable bowel syndrome, inflammatory bowel disease, celiac disease, and colorectal cancer. Understanding the role of the oral-to-gut microbial translocation in the pathogenesis will contribute to precise diagnosis and effective treatment. In this review, we aim to highlight the role of oral microbiota dysfunction in various gastrointestinal disorders.