Hyperglycemia and metabolic syndrome (MetS) are common in patients with major depressive disorder (MDD). This study aimed to explore the prevalence and clinical factors of MetS in first-episode and drug-naive MDD (FEDND) patients with and without hyperglycemia. A total of 1,718 FEDND patients' symptoms were assessed using the Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), and positive subscale of the Positive and Negative Syndrome Scale (PANSS). Blood glucose levels, metabolic index, and thyroid hormones were measured during fasting. The prevalence of MetS in FEDND patients with hyperglycemia was 35.67 times higher than in FEDND patients without hyperglycemia. FEDND patients with MetS were older, had later age of onset, and were predominantly married than those without MetS (p < 0.05). Among FEDND patients without hyperglycemia, suicide attempts, severe anxiety, HAMD, HAMA, PANSS subscale scores, thyroid stimulating hormone, antithyroglobulin, and total cholesterol levels were all higher in patients with MetS than those without MetS (all p < 0.05). In FEDND patients without hyperglycemia, the combination of age and TgAb distinguished those patients with and without MetS. Our results suggest a high prevalence of MetS in FEDND patients with hyperglycemia. Several clinical variables and thyroid function-related hormones impact MetS in patients with FEDND.