BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with a high risk of cardiovascular mortality, primarily from coronary heart disease (CHD). Thyroid hormone (TH) sensitivity and albumin independently influence cardiovascular health and metabolic homeostasis. However, the potential mediating role of albumin in the association between TH sensitivity and the risk of CHD remains unclear in patients with T2DM. METHODS: This cross-sectional study enrolled 430 hospitalized T2DM patients, categorized into CHD and non-CHD groups. Central TH sensitivity was evaluated using the thyrotrophic thyroxine resistance index (TT4RI), thyroid-stimulating hormone index (TSHI), thyroid feedback quantile index (TFQI), and parametric thyroid feedback quantile index (PTFQI). Peripheral TH sensitivity was estimated by the free triiodothyronine to free thyroxine (FT3/FT4) ratio. Logistic regression, restricted cubic spline and receiver operating characteristic curve were performed. Mediation analysis quantified the indirect effects of serum albumin. RESULTS: Compared to non-CHD patients, the CHD group exhibited significantly diminished FT3/FT4 ratio and albumin levels. Multivariate logistic regression indicated that a decreased FT3/FT4 ratio was independently associated with CHD, whereas central TH sensitivity indices showed no significant correlation. The FT3/FT4 ratio exhibited the modest discriminative ability for CHD (AUC = 0.740). Furthermore, albumin partially mediated the association between peripheral TH sensitivity and CHD, accounting for 19.3% of the total effect. CONCLUSIONS: Impaired peripheral thyroid hormone sensitivity is positively associated with CHD in T2DM and serum albumin might be one of its biological mechanisms.