The purpose of this study was to analyse whether the nationwide application of the national Serbian guideline for diabetes mellitus (NSGDM) would save a relevant amount of disability-adjusted life years (DALYs) and/or reduce the medical cost of treating diabetic patients in Serbia, as compared to the present situation. Disability-adjusted life years were calculated for Serbia and the cost-effectiveness was analysed in eight population groups under ideal and present conditions; prevalent and incident cases were each split up for patients with blood glucose that was well controlled and that was uncontrolled. Under ideal conditions, i.e., according to the NSGDM, 8,031 DALYs could be saved with a potential cost reduction at the same time of approximately 19 million Euros. The implementation of the NSGDM in clinical practice bears a great potential to save lives and reduce years lived with lowered quality of life, but in addition it may reduce costs by about a quarter.