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Abstract: Optogenetics combines optics and genetic engineering to control specific gene expression and biological functions and has the advantages of precise spatiotemporal control, noninvasiveness, and high efficiency. Genetically modified photosensory sensors are engineered into proteins to modulate conformational changes with light stimulation. Therefore, optogenetic techniques can provide new insights into oral biological processes at different levels, ranging from the subcellular and cellular levels to neural circuits and behavioral models. Here, we introduce the origins of optogenetics and highlight the recent progress of optogenetic approaches in oral and craniofacial research, focusing on the ability to apply optogenetics to the study of basic scientific neural mechanisms and to establish different oral behavioral test models in vivo (orofacial movement, licking, eating, and drinking), such as channelrhodopsin (ChR), archaerhodopsin (Arch), and halorhodopsin (NpHR). We also review the synergic and antagonistic effects of optogenetics in preclinical studies of trigeminal neuralgia and maxillofacial cellulitis. In addition, optogenetic tools have been used to control the neurogenic differentiation of dental pulp stem cells in translational studies. Although the scope of optogenetic tools is increasing, there are limited large animal experiments and clinical studies in dental research. Potential future directions include exploring therapeutic strategies for addressing loss of taste in patients with coronavirus disease 2019, studying oral bacterial biofilms, enhancing craniomaxillofacial and periodontal tissue regeneration, and elucidating the possible pathogenesis of dry sockets, xerostomia, and burning mouth syndrome.