BackgroundMachine learning (ML) through artificial intelligence (AI) could provide clinicians and oral pathologists to advance diagnostic problems in the field of potentially malignant lesions, oral cancer, periodontal diseases, salivary gland disease, oral infections, immune-mediated disease, and others. AI can detect micro-features beyond human eyes and provide solution in critical diagnostic cases.ObjectiveThe objective of this study was developing a software with all needed feeding data to act as AI-based program to diagnose oral diseases. So our research question was: Can we develop a Computer-Aided Software for accurate diagnosis of oral diseases based on clinical and histopathological data inputs?MethodThe study sample included clinical images, patient symptoms, radiographic images, histopathological images and texts for the oral diseases of interest in the current study (premalignant lesions, oral cancer, salivary gland neoplasms, immune mediated oral mucosal lesions, oral reactive lesions) total oral diseases enrolled in this study was 28 diseases retrieved from the archives of oral maxillofacial pathology department. Total 11,200 texts and 3000 images (2800 images were used for training data to the program and 100 images were used as test data to the program and 100 cases for calculating accuracy, sensitivity& specificity).ResultsThe correct diagnosis rates for group 1 (software users), group 2 (microscopic users) and group 3 (hybrid) were 87%, 90.6, 95% respectively. The reliability for inter-observer value was done by calculating Cronbach’s alpha and interclass correlation coefficient. The test revealed for group 1, 2 and 3 the following values respectively 0.934, 0.712 & 0.703. All groups showed acceptable reliability especially for Diagnosis Oral Diseases Software (DODS) that revealed higher reliability value than other groups. However, The accuracy, sensitivity & specificity of this software was lower than those of oral pathologists (master’s degree).ConclusionThe correct diagnosis rate of DODS was comparable to oral pathologists using standard microscopic examination. The DODS program could be utilized as diagnostic guidance tool with high reliability & accuracy.