Medication adherence is a critical component in the management of diabetes mellitus, yet non-adherence remains a major challenge, leading to poor glycaemic control and increased risk of complications. This study examined the role of nurses in promoting medication adherence among patients with diabetes mellitus at the Government General Hospital in Cross River State, Nigeria. The objectives were to determine the level of medication adherence among patients, identify the roles and interventions of nurses in promoting adherence, and explore the challenges nurses face in ensuring consistent medication use. A descriptive survey design was employed, involving a purposive sample of 159 registered nurses and 100 adult patients diagnosed with diabetes mellitus. Data were collected using structured questionnaires and analyzed with descriptive statistics, Pearson correlation, and thematic content analysis for qualitative responses. The results revealed that only 30 percent of patients demonstrated high adherence, while 45 percent and 25 percent showed medium and low adherence, respectively. Nurses’ interventions, such as patient education, counseling, monitoring, and follow-ups, were significantly associated with improved medication adherence with a correlation coefficient of 0.612 and a p-value of 0.001. Conversely, challenges faced by nurses, including high patient-to-nurse ratios, limited resources, and patient-related factors, were negatively associated with adherence with a correlation coefficient of -0.543 and a p-value of 0.002. The study concluded that nurses play a pivotal role in promoting medication adherence, but systemic and professional challenges limit their effectiveness. The findings highlight the need for institutional support, continuous training, structured adherence programs, and patient-centered strategies to enhance adherence and improve health outcomes among patients with diabetes mellitus.