Aim: This study compares health-related quality of life (HRQL) in patients with type 2 diabetes (T2DM) across treatment groups and explores gender differences. Methods: Four regional surveys (KORA, CARLA, SHIP, DHS) and a national survey (GNHIES98) were pooled at individual level. HRQL was assessed with the SF-12/-36v1. Linear regression models were used to assess the effect of T2DM by treatment type (no medication; oral; oral/insulin combination; insulin) on the physical (PCS-12) and mental summary score (MCS-12) and the SF-6D, controlling for age, sex, study and covariates. We also performed an explanatory analysis of single items. Results: PCS-12 scores and treatment type were associated (P-value 0.006), with lowest values for insulin treatment (-4.44 vs. oral; -4.41 vs. combination). MCS-12 scores were associated with treatment type and gender (P-value <. 0.012), with lower scores for women undergoing oral (-4.25 vs. men) and combination treatment (-6.99 vs. men). Similar results were observed for SF-6D utilities and single items, related to mental health, social functioning, vitality and role limitation (emotional). Comorbidities were predictors of lower PCS-12 and SF-6D scores. Conclusions: T2DM treatment impacts differently on physical and mental HRQL and on women and men. Further studies of gender-specific perceptions of T2DM treatment regimens are needed.