Objective: The aim of this study was to assess the treatment adherence for DM as related to quality of life and to assess the factors contributing to non-adherence among the types 1 and 2 diabetes patients in the Asser Region, Saudi Arabia. Patients and methods: A cross-sectional study was carried out on 200 DM patients. An eight-item Morisky medication adherence questionnaire was used to assess adherence. A validated questionnaire was used to collect information on factors influencing non-adherence. The percentage of adherence and the factors contributing to non-adherence were analysed with descriptive statistics, chi-square test and independent sample t-test. Results: The current study showed that the overall prevalence of therapeutic non-adherence was 76 patients (38%). Among the non-adherent patients, (28.9%) patients were illiterate, 40 had economic problems which prohibited their purchase of the prescribed medicines (p=0.56), (26%) patients were aware of the outcomes if the medications were not taken regularly (p=0.591), most of the patients (56, 28.6%) were not aware of the common side effects of their medications (p = 0.606), (23.5%) of the patients were not exercising regularly (p=0.651), (20%) patients of the low adherent patients were afraid of hypoglycaemia and (42.9%) patients were suffering from forgetfulness in regard to taking their medication. Conclusion: The current study suggests acceptable level of adherence among diabetic patients in Aseer region, Saudi Arabia. The study finding that the most common barriers to patients' adherence were forgetfulness, fear of hypoglycaemia, weight gain and difficulties with injections.