Introduction Periodontitis is an oral inflammatory disease of significant importance, that leads to gingival inflammation, alveolar bone loss and has a high impact on the quality of life and general health. There has been a continuous interest in the scientific world to test new therapies and therapeutic materials for periodontal disease. One of the most critical tools to investigate mechanisms of periodontal pathogenesis and test new therapeutic materials are animal models. In addition, there is a wide range of materials used in periodontal therapy, especially in terms of bone augmentation, so choosing the ideal material is often difficult to achieve. Methodology In this article, we have evaluated two methods for testing artificially induced periodontal defects - intra-orally and extra-orally - the biological adaptation of the materials used in periodontal and bone regeneration techniques on animal models. Results We have created two protocols for the extra-oral and intra-oral approaches. By following them we have succesfully managed to create the periodontal defects and to apply the therapeutic materials. We have also made a comparison between the two methods, and the possibilities of materials that can be used. Conclusion Tests performed on animal models will remain an important asset for evaluating new approaches for the improvement of tissue regeneration therapies. As there are continuous advances in the study of dental materials, we also have to search for new, easy to perform, ethics-friendly methods to evaluate the biological response of these materials.