Oral potentially malignant disorders (OPMDs) are a heterogeneous group of oral lesions with a variable risk of malignant transformation to oral squamous cell carcinoma. The current OPMDs malignant transformation screening depends on conventional oral examination (COE) and is confirmed by biopsy and histologic examination. However, early malignant lesions with subtle mucosal changes are easily unnoticed by COE based on visual inspection and palpation. Optical techniques have been used to determine the biological structure, composition, and function of cells and tissues noninvasively by analyzing the changes in their optical properties. The oral epithelium and stroma undergo persistent structural, functional, and biochemical alterations during malignant transformation, leading to variations in optical tissue properties; optical techniques are thus powerful tools for detecting OPMDs malignant transformation. The optical imaging methods already used to detect OPMDs malignant transformation in vivo include autofluorescence imaging, narrowband imaging, confocal reflectance microscopy, and optical coherence tomography. They exhibit advantages over COE in detecting biochemical or morphologic changes at the molecular or cellular level in vivo; however, limitations also exist. This article comprehensively reviews the various real-time in vivo optical imaging methods used in the adjunctive diagnosis of OPMDs malignant transformation. We focus on the principles of these techniques, review their clinical application, and compare and summarize their advantages and disadvantages. Finally, we conclude with a discussion of current challenges and future directions of this field.