The use of bioactive materials has become a standard tool in the arsenal of tissue engineering and regenerative medicine applications. Bioactive materials have gained great attention due to their ability to mimic tissues physically, chemically and mechanically. Although a plethora of both natural and synthetic polymers have been identified, wool-based keratin which has a natural propensity to self-assemble, is biocompatible, cytocompatible, biodegradable, non-toxic and non-immunogenic, can also diminish the adhesion and growth of bacterial biofilm. Keratin based materials have been subsequently been applied in various tissue engineering applications from wound healing to drug and growth factor delivery to bone regeneration. This review focuses on the key properties of keratin including porosity and pore size, swelling rate, degradation rate, wettability and mechanical properties responsible for its biofunctional activity, as well as recent advances in keratin-based biomaterials for biomedical applications.