BACKGROUND: Diabetes mellitus (DM) is a major health-care burden worldwide. AIM: The aim of the study was to explore how the quality of life (QoL) of DM patients could be affected in the Aseer Province of the Kingdom of Saudi Arabia (KSA). METHODS: A cross-sectional, multicenter study in DM patients of both sexes and all age groups in Aseer Province were done using a validated self-administered questionnaire. The study was conducted between April 1, 2018 and November 25, 2018. RESULTS: A total of 418 patients completed our questionnaire, of which 240 (58%) were male and 178 (42%) were female. Furthermore, 50.23% were married and 104 (24.16%) were illiterate. We found that 403 (96.42%) respondents had type-2 DM and 315 (75.35%) had a family history of DM. In addition, 132 (31.57%) respondents were on monotherapy whereas only 61 (14.59%) were using combination therapy. Hypertension was the most prevalent comorbidity (166, 39.71%) and peripheral neuropathy the most prevalent complication of DM (157, 37.56%). CONCLUSION: DM had a significant impact on QoL among patients from Aseer Province in KSA. Our study underscores the importance of generating data on QoL among DM patients.