Oral premalignant lesions (OPMLs) constitute a heterogeneous group of mucosal disorders with varying risks of malignant transformation into oral squamous cell carcinoma (OSCC). Early detection of dysplastic alterations remains crucial for improving prognosis and reducing mortality. Conventional cytological evaluation relies primarily on subjective morphological interpretation, which may lead to interobserver variability. Quantitative cytomorphometric analysis provides an objective, reproducible, and computer-assisted method for evaluating cellular and nuclear alterations associated with disease progression. Parameters such as nuclear area, cytoplasmic area, nuclear diameter, nuclear perimeter, nuclear-cytoplasmic ratio, form factor, and chromatin density have demonstrated significant changes during the progression from normal mucosa to epithelial dysplasia and carcinoma. Advances in digital pathology, artificial intelligence, image analysis software, and machine learning have further enhanced the diagnostic utility of cytomorphometry. This review summarizes the biological basis, methodology, diagnostic applications, advantages, limitations, and future prospects of quantitative cytomorphometric analysis in oral premalignant lesions.