Background <p>Diabetes mellitus significantly impairs quality of life (QoL), yet comparative data between type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) in resource-limited, conflict-affected settings such as Palestine remain scarce, particularly for adults with T1DM.</p> Aim <p>This study assessed QoL among adults with diabetes in southern Palestine, compared outcomes between T1DM and T2DM, and identified demographic and clinical predictors influencing QoL.</p> Methods <p>A cross-sectional study using convenience sampling was conducted among 393 adults recruited from diabetes clinics and healthcare centers in the southern West Bank. QoL was measured using the Revised Diabetes Quality of Life Questionnaire (RVDQOL-13). Statistical analyses included independent samples t-tests, Pearson correlation, and multiple linear regression.</p> Results <p>Overall QoL showed moderate impairment (M = 44.07, SD = 13.47), with no significant difference between participants with T1DM and T2DM. However, individuals with T1DM reported significantly poorer satisfaction scores than those with T2DM (<i>p</i> = 0.001). Regression analysis indicated that physical activity was significantly associated with QoL among participants with T1DM. In contrast, female gender, lower physical activity, higher HbA1c levels, and diabetic foot complications were significantly associated with poorer QoL among participants with T2DM.</p> Conclusion <p>Palestinian adults with T1DM and T2DM experience comparable overall QoL impairment; however, T1DM is associated with poorer treatment satisfaction. Targeting modifiable factors, particularly physical activity, glycemic control, and foot complications, may provide important opportunities for improving QoL through primary care interventions, especially for individuals with T2DM who are at higher risk of these complications.</p>