The oral and gastrointestinal microbiomes are increasingly recognized as interconnected ecological systems rather than isolated microbial communities. The oral cavity harbors diverse biofilm-associated microbial populations that are continuously introduced into the gastrointestinal tract through saliva, shed biofilms, and swallowed planktonic bacteria. Under homeostatic conditions, gastric acidity, bile, antimicrobial peptides, epithelial barriers, and resident gut microbiota limit the persistence of oral microbes. However, disruption of colonization resistance by inflammation, antibiotics, proton-pump inhibitors, immunosuppression, diet, or host susceptibility may allow oral-derived taxa to persist or engraft within the gut. This oral–gut microbiome axis is mediated through microbial migration, immune signaling, metabolite exchange, epithelial barrier disruption, and inflammatory feedback loops. Growing evidence links oral dysbiosis and periodontal inflammation with gastrointestinal disorders, including inflammatory bowel disease, irritable bowel syndrome, celiac disease, colitis, and colorectal cancer, as well as systemic diseases such as cardiovascular disease, metabolic disorders, neurodegenerative diseases, and autoimmune conditions. Among these, inflammatory bowel disease and colorectal cancer currently have the strongest mechanistic and translational support. Oral microbiome-based biomarkers, particularly from saliva and oral swabs, also show promise for non-invasive screening, disease monitoring, risk prediction, and personalized intervention. Nevertheless, many associations remain context-dependent, and causality is not fully established. Future progress will require longitudinal cohorts, standardized sampling pipelines, mechanistic validation, and integration of microbial, metabolic, immune, and clinical data. Understanding the oral–gut axis may expand current approaches to prevention, diagnosis, and precision management of gastrointestinal and systemic diseases.