Tissue engineering is a new therapeutic strategy used to repair serious damage caused by trauma, a tumor or other major diseases, either for vital organs or tissues sited in the oral cavity. Scaffold materials are an indispensable part of this. As an extracellular-matrix-based bio-material, treated dentin matrixes have become promising tissue engineering scaffolds due to their unique natural structure, astonishing biological induction activity and benign bio-compatibility. Furthermore, it is important to note that besides its high bio-activity, a treated dentin matrix can also serve as a carrier and release controller for drug molecules and bio-active agents to contribute to tissue regeneration and immunomodulation processes. This paper describes the research advances of treated dentin matrixes in tissue regeneration from the aspects of its vital properties, biologically inductive abilities and application explorations. Furthermore, we present the concerning challenges of signaling mechanisms, source extension, individualized 3D printing and drug delivery system construction during our investigation into the treated dentin matrix. This paper is expected to provide a reference for further research on treated dentin matrixes in tissue regeneration and better promote the development of relevant disease treatment approaches.