This systematic review elucidates the complex interplay between gastroesophageal reflux disease (GERD) and diabetes mellitus, integrating findings from various studies to highlight pathophysiological connections and effective clinical management strategies. Our examination reveals that mechanisms such as delayed gastric emptying and autonomic neuropathy significantly contribute to the exacerbation of GERD symptoms in diabetic patients, influencing clinical outcomes and treatment efficacy. The review underscores the necessity of multidisciplinary approaches in treating these comorbid conditions and advocates for therapeutic strategies that simultaneously address GERD and diabetes, such as the use of prokinetic agents and tailored surgical interventions like laparoscopic Roux-en-Y gastric bypass. This synthesis advances our understanding and proposes a foundation for future research and clinical practice, aiming to improve the quality of life and treatment outcomes for affected patients. This work contributes significantly to gastroenterology and endocrinology, providing a comprehensive resource for clinicians and researchers alike.