Type Ⅱ deiodinase (D2) is an important selenium-containing protease responsible for the outer ring deiodination of thyroxine (T₄) to form the more biologically active triiodothyronine (T₃), thereby regulating metabolism, growth and development, and energy balance in the body. D2 activity is regulated by various factors, including thyroid hormone levels, the cAMP pathway, ubiquitination, endoplasmic reticulum stress, and environmental factors. D2 is closely related to the occurrence and development of thyroid diseases and plays a crucial role in regulating cell proliferation, thus it is considered a potential cancer marker. Additionally, the Thr92Ala polymorphism of the type Ⅱ deiodinase gene (DIO2) has been confirmed as a factor related to thyroid diseases. Understanding the relationship between this polymorphism and thyroid diseases can help predict individual disease risk and provide a basis for personalized treatment. This review focuses on the regulatory mechanisms of D2 and its essential role in thyroid diseases, as well as the impact of the DIO2 Thr92Ala polymorphism on disease development, to provide a guidance for future research and clinical praxis.