Objective: To explore the association between 25-hydroxyvitamin D [25(OH)D] and clinical indicators in patients with type 2 diabetes mellitus (T2DM) combined with Hashimoto’s thyroiditis (HT). Methods: We selected 100 patients with T2DM combined with HT, 100 patients with T2DM and 100 healthy subjects, and collected general data such as age, sex, height, and weight of all study subjects, and measured fasting blood-glucose (FBG), blood lipids, liver function, HbA1c, free triiodothyronine 3 (FT₃), free thyroxine (FT₄), thyroid stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TGA), and thyroid glucose. We also explored the correlation between 25(OH)D and each group of indicators and analyzed the possible mediators among them using a mediating effect model. Results: In the T2DM + HT group, HbA1c, C-reactive protein (CRP), TPOAb, TGAb and TG were negatively correlated with 25(OH)D, high-density lipoprotein cholesterol (HDL-C) was positively correlated with 25(OH)D, and CRP mediated 20.04% of the effect of 25(OH)D in causing a decrease in HbA1c. Meanwhile, HbA1c mediated 12.04% of the effect during the reduction of TGAb due to 25(OH)D. Conclusion: 25(OH)D affects disease progression in T2DM + HT patients, with CRP and HbA1c playing an important role in the process.