It is widely accepted that diabetes mellitus due to its related complications causes an important decrease in health-related quality of life (HRQOL). This study aimed to analyze the influence of gender on HRQOL in patients with type 2 diabetes mellitus (T2D). The SF-36v2 questionnaire was administered to 95 individuals with T2D (47 women and 48 men; 66.23 ± 6.34 years old) and comparisons by gender were performed for each SF-36v2 scale (physical functioning, PF; role physical, RP; bodily pain, BP; general health, GH; vitality, VT; social functioning, SF; role emotional, RE; mental health, MH) and summary scales (physical component score, PCS; mental component score, MCS). Significant differences were observed between women and men on the scales PF (65.32 ± 21.35 vs. 78.44 ± 19.92, p = 0.003), BP (58.72 ± 29.65 vs. 75.10 ± 26.35, p = 0.005), VT (57.87 ± 23.56 vs. 70.73 ± 19,24, p = 0.004), SF (79.79 ± 20.61 vs. 88.02 ± 16.50, p = 0.034), RE (75.00 ± 23,18 vs. 85.76 ±18,35, p = 0.014), MH (65.96 ± 23.38 vs. 79.00 ± 14.04, p = 0.001), and summary scales PCS (42.93 ± 9.95 vs. 47.33 ± 9.92, p = 0.034) and MCS (51.19 ± 9.65 vs. 55.03 ± 7.46, p = 0.032). Our results suggest that women with T2D report lower values than men on most of the HRQOL scales and that special attention should be given to these women\\\\\\\'s well-being needs.