The oral and craniofacial region consists of various types of hard and soft tissues with the intricate organization. With the high prevalence of tissue defects in this specific region, it is highly desirable to enhance tissue regeneration through the development and use of engineered biomaterials. Collagen, the major component of tissue extracellular matrix, has come into the limelight in regenerative medicine. Although collagen has been widely used as an essential component in biomaterial engineering owing to its low immunogenicity, high biocompatibility, and convenient extraction procedures, there is a limited number of reviews on this specific clinic sector. The need for mechanical enhancement and functional engineering drives intensive efforts in collagen-based biomaterials concentrating on therapeutical outcomes and clinical translation in oral and craniofacial tissue regeneration. Herein, we highlighted the status quo of the design and applications of collagen-based biomaterials in oral and craniofacial tissue reconstruction. The discussion expanded on the inspiration from the leather tanning process on modifications of collagen-based biomaterials and the prospects of multi-tissue reconstruction in this particular dynamic microenvironment. The existing findings will lay a new foundation for the optimization of current collagen-based biomaterials for rebuilding oral and craniofacial tissues in the future. Graphical Abstract: [Figure not available: see fulltext.] © 2023, The Author(s).