Objectives To examine the validity and reliability of the Menopause-specific Quality of Life (MENQOL) questionnaire in a sample of women with diabetes in Malaysia, with the secondary aim of determining whether MENQOL domain scores were associated with depression and diabetes. Methods A total of 337 postmenopausal women (241 with diabetes, 96 controls) were evaluated. Construct validity was evaluated using principal components analysis (PCA) and comparing scale items against the mental component score of the Short Form-12 (SF-12 MCS), and against the Center for Epidemiologic Studies Depression Scale 10 (CES-D 10). Consistency assessment was conducted using Cronbach's α. Results The internal consistencies for the physical (PHS), psychosocial (PS), sexual (VSS) and vasomotor domains were 0.86, 0.79, 0.79 and 0.70, and 0.90 for the full scale of MENQOL. PCA revealed a four-factorial model. Diabetes and non-diabetes subjects experienced their first period (13.25 vs. 13.10 years, p = 0.680) and achieved menopause around the same age (49.35 vs. 48.87 years, p = 0.426). We found significant variations in the MENQOL's PHS and PS domain scores that could be explained by SF-12 PCS (25%) and SF-12 MCS (20%) sub-scales. The validity of the MENQOL domains was demonstrated through significant associations with the equivalent SF-12 MCS and PCS subscales. The PS domain of the MENQOL also predicted the likelihood of symptoms of depression (1.42, 95% confidence interval 1.01-2.02). Conclusions This study confirms the validity and internal consistency of the MENQOL questionnaire for measuring quality of life in postmenopausal women with diabetes, suggesting that the instrument can be used to screen people for menopausal symptoms.