Background: Biotechnology shows a promising future in bridging the gap between biomedical basic sciences and clinical craniofacial practice. The purpose of the present review is to investigate the applications of biotechnology in the craniofacial complex. Methods: This critical review was conducted by using the following keywords in the search strategy: “biotechnology”, “bioengineering”, “craniofacial”, “stem cells”, “scaffolds”, “biomarkers”, and ”tissue regeneration”. The databases used for the electronic search were the Cochrane Library, Medline (PubMed), and Scopus. The search was conducted for studies published before June 2022. Results: The applications of biotechnology are numerous and provide clinicians with the great benefit of understanding the etiology of dentofacial deformities, as well as treating the defected areas. Research has been focused on craniofacial tissue regeneration with the use of stem cells and scaffolds, as well as in bioinformatics with the investigation of growth factors and biomarkers capable of providing evidence for craniofacial growth and development. This review presents the biotechnological opportunities in the fields related to the craniofacial complex and attempts to answer a series of questions that may be of interest to the reader. Conclusions: Biotechnology seems to offer a bright future ahead, improving and modernizing the clinical management of cranio-dento-facial diseases. Extensive research is needed as human studies on this subject are few and have controversial results.