Oral and maxillofacial diseases can happen in many different tissues, including teeth, mucosa, muscle, bone, and cartilage. Investigation of the pathology and intervention for oral and maxillofacial diseases in disease models is important. New surgical techniques, biomaterials, and drugs are developing for the better day by day. Before final translation and application in treating patients, in vitro and in vivo studies are necessary. However, there is significant difficulty in disease model establishment for oral and maxillofacial diseases. For example, the structures of the oral and maxillofacial regions of common animals for experiments are too small, and tissues involved in oral and maxillofacial diseases are always complex. The requirement for consummate skill guarantees the success of model establishment for oral and maxillofacial disease. This process may be accompanied by the possibility of unsatisfactory effect or failure and avoiding these failures will improve the quality and reliability of the research. Although the establishment of the disease model is designed according to the study objectives, which still needs to be modified based on the standard model. Therefore, demonstrating the process for a standard disease model establishment, both in vitro and in vivo, will provide a more stable and reliable basis for improving the treatment for oral and maxillofacial diseases. We encourage the authors to present the specific steps of the disease model establishment and discuss how to make it successful. This collection will include methodologies for the model establishment both in vitro and in vivo for studying oral and maxillofacial diseases.