The accuracy of artificial intelligence (AI)-assisted discrimination of oral cancerous lesions from normal mucosa based on mucosal images was evaluated. Two authors independently reviewed the database until June 2022. Oral mucosal disorder, as recorded by photographic images, autofluorescence, and optical coherence tomography (OCT), was compared with the reference results by histology findings. True-positive, true-negative, false-positive, and false-negative data were extracted. Seven studies were included for discriminating oral cancerous lesions from normal mucosa. The diagnostic odds ratio (DOR) of AI-assisted screening was 121.66 (95% confidence interval [CI], 29.60; 500.05). Twelve studies were included for discriminating all oral precancerous lesions from normal mucosa. The DOR of screening was 63.02 (95% CI, 40.32; 98.49). Subgroup analysis showed that OCT was more diagnostically accurate (324.33 vs. 66.81 and 27.63) and more negatively predictive (0.94 vs. 0.93 and 0.84) than photographic images and autofluorescence on the screening for all oral precancerous lesions from normal mucosa. Automated detection of oral cancerous lesions by AI would be a rapid, non-invasive diagnostic tool that could provide immediate results on the diagnostic work-up of oral cancer. This method has the potential to be used as a clinical tool for the early diagnosis of pathological lesions.