Gastrointestinal (GI) symptoms are common in patients with end-stage renal disease; although they are often considered a natural part of the dialysis process, these symptoms have significant effects on clinical outcomes. Nausea, vomiting, loss of appetite, constipation, diarrhea, reflux, and gastrointestinal bleeding can impair nutritional status, exacerbate malnutrition, reduce dialysis tolerance, and increase hospitalization rates. Therefore, GI symptoms should be addressed not as an isolated issue but as important clinical indicators signaling a disruption in systemic balance. From a pathophysiological perspective, the accumulation of uremic toxins, intradialytic hemodynamic fluctuations, medication load, and changes in the intestinal microbiota multifacetedly affect GI function. In particular, while intradialytic hypotension and splenic hypoperfusion play a critical role in symptom development, medication-related mucosal sensitivity and the risk of bleeding must also be considered. In clinical management, the timing, severity, and relationship of symptoms to dialysis parameters should be systematically evaluated. Nursing care should be structured around early recognition, regular monitoring, patient education, and effective communication with the multidisciplinary team. The measurable monitoring of symptoms and their integration into the care plan play a fundamental role in enhancing treatment efficacy. In conclusion, managing gastrointestinal symptoms using a comprehensive and evidence-based approach is of critical importance for improving patient safety, quality of life, and clinical outcomes.