We aimed to examine the association between metabolic syndrome (MetS), depressive symptoms, and health-related quality of life in postmenopausal women. We conducted a descriptive cross-sectional study in naturally postmenopausal women aged 45-65 years using data from the 8th Korea National Health and Nutrition Examination Survey. We classified the participants into four groups: normal (neither MetS nor depressive symptoms), MetS, depressive symptoms, and MetS + depressive symptoms. Compared to the other three groups, the MetS + depressive symptoms group had the worst self-rated health. High fasting glucose, high triglyceride and low high-density lipoprotein-cholesterol levels were the most common in the MetS + depressive symptoms group. After adjusting for covariates, the MetS + depressive symptoms group was more likely to have problems with usual activities and pain/discomfort than the normal group.