Background and Objectives: Distinguishing cancer from precancerous lesions is critical and challenging in oral medicine. As a noninvasive method, optical coherence tomography (OCT) has the advantages of real-time, in vivo, and large-depth imaging. Texture information hidden in OCT images can provide an important auxiliary effect for improving diagnostic accuracy. The aim of this study is to explore a reliable and accurate OCT-based method for the screening and diagnosis of human oral diseases, especially oral cancer. Materials and Methods: Fresh ex vivo oral tissues including normal mucosa, leukoplakia with epithelial hyperplasia (LEH), and oral squamous cell carcinoma (OSCC) were imaged intraoperatively by a homemade OCT system, and 58 texture features were extracted to create computational models of these tissues. A principal component analysis algorithm was employed to optimize the combination of texture feature vectors. The identification based on artificial neural network (ANN) was proposed and the sensitivity/specificity was calculated statistically to evaluate the classification performance. Results: A total of 71 sites of three types of oral tissues were measured, and 5176 OCT images of three types of oral tissues were used in this study. The superior classification result based on ANN was obtained with an average accuracy of 98.17%. The sensitivity and specificity of normal mucosa, LEH, and OSCC are 98.17% / 98.38%, 93.81% / 98.54%, and 98.11% / 99.04%, respectively. Conclusion: It is demonstrated from the high accuracies, sensitivities, and specificities that texture-based analysis can be used to identify oral precancerous and cancerous tissue in OCT images, and it has the potential to help surgeons in diseases screening and diagnosis effectively.