Ulcerative colitis (UC) and gastroesophageal reflux disease (GERD) are two prevalent gastrointestinal disorders, affecting the intestinal tract and the esophagus-stomach region, respectively. However, recent studies have revealed potential intricate connections between them in terms of pathophysiological mechanisms, shared risk factors, pharmacological impacts, and complications. This review systematically synthesizes the latest research advancements, with a particular focus on the pivotal role of gut microbiota in the interplay between UC and GERD. Research findings suggest that impaired intestinal barrier function, neuroendocrine dysregulation, and gut microbiota-mediated immune-inflammatory responses may constitute the core mechanisms underlying the co-pathogenesis of these two conditions. Furthermore, shared risk factors such as diet, psychological factors, and medication use exacerbate their mutual influence. This review aims to provide a theoretical foundation for clinical diagnosis and treatment, and calls for future research to delve deeper into the molecular mechanisms of gut microbiota in the association between UC and GERD, thereby paving new avenues for the prevention and treatment of gastrointestinal diseases.