Abstract: Thietane, as a four-membered heterocyclic structure, has demonstrated broad application prospects in the development of antitumor, anti-inflammatory, antibacterial, and antiviral drugs in recent years due to its unique structural characteristics and superior properties. This article reviews the recent progress in active compounds containing thietane structures and their applications in the treatment of various diseases, exploring the advantages of thietane in drug design, including its role as a bioisostere and its impact on drug metabolic stability and solubility. By summarizing the applications of thietane in medicinal chemistry, this article provides new insights and directions for future drug design.