Metabolic syndrome (MetS) is a condition that includes a cluster of risk factors for cardiovascular disease. In this paper, we aimed to evaluate the association between depressive symptoms, antidepressant use, duration of antidepressant use, antidepressant type and MetS. Data from the 2005-2018 National Health and Nutrition Examination Surveys were used in this study. Adults were included if they responded to the depressive symptoms and prescription medications questionnaires and had measures of blood pressure, waist circumference, triglycerides, high-density lipoprotein, and fasting plasma glucose. Participants were categorized by their antidepressant use (yes/no), type, and duration. This study included 14,875 participants (50.45% females), with 3616 (23.45%) meeting the criteria for MetS. Participants with higher depressive symptom scores (aOR = 1.04, 95% CI: 1.02, 1.05, p <
0.001) or those with depressive symptoms (aOR = 1.42, 95% CI: 1.17, 1.73, p = 0.001) had higher odds of MetS. A similar associations was seen among those who were on antidepressants compared to those who were not on antidepressants (aOR = 1.24, 95% CI: 1.03, 1.50, p = 0.025). Duration of antidepressant use was not significantly associated with MetS. Participants on tricyclic antidepressants had greater odds of MetS compared to those not taking any antidepressants (aOR = 2.27, 95% CI: 1.31, 3.93, p = 0.004). Our study provides evidence of the association between depressive symptoms, antidepressant use, and MetS, highlighting the importance of monitoring metabolic and cardiovascular alterations in individuals of depression.