Background: Oral cancer is a major global health concern, with over 11 million new cases and 6 million deaths annually. Early detection and metastasis prediction are crucial. Objectives: Evaluate serum and salivary LDH levels in oral cancer patients, individuals with potentially malignant disorders, tobacco users, and healthy controls. Methods: 120 participants were divided into four groups. Saliva and serum samples (2 ml each) were collected, stored at ‑20°C, and analyzed using an LDH kit on a semi-auto analyzer. One-way ANOVA and Pearson’s correlation were used for statistical analysis. Results: Salivary LDH levels differed significantly among groups (Controls: 82.00 IU/L, Tobacco users: 106.97 IU/L, Potentially malignant: 157.23 IU/L, Oral cancer: 193.73 IU/L, P < 0.05). Pearson correlation was positive for oral cancer, potentially malignant, and healthy groups; negative for tobacco users. Conclusion: Salivary LDH is preferable to serum LDH for early detection and monitoring of oral cancer and potentially malignant disorders, offering a non-invasive method. © 2024 Elsevier B.V., All rights reserved.