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Introduction: Oral submucous fibrosis (OSMF) is a chronic, mild, possibly malignant condition (OPMD) that primarily affects South Asian people, affecting the oral cavity and oropharynx. Clinically, trismus, restricted tongue protrusion, burning mouth, marble-like oral mucosa appearance, xerostomia, recurrent ulceration, atrophy of the tongue papillae, and palpable fibrous bands are among the symptoms and indicators of OSMF. The present study was undertaken to determine the salivary levels of oxidative stress biomarkers malondialdehyde, 8-hydroxy-2-deoxyguanosine and 8-isoprostane levels and antioxidants glutathione peroxidase and superoxide dismutase in patients with different grades of OSMF. Methodology: The observational cross-sectional study was conducted in the department of Biochemistry NIMS&R, Jaipur in association with Oral Diagnosis and Radiology at College of Dental Sciences and Research Centre, Manipur, Ahmedabad (Gujarat) after obtaining institutional ethical committee clearance. The Study population consisted of Clinically diagnosed oral submucous fibrosis patients of age 18-45 years. Unstimulated Saliva was allowed to accumulate in the floor Of mouth and collected by drooling method in a test tube. Saliva samples will be stored at -20 °C until use. Malondialdehyde was estimated by thiobarbituric acid reaction using spectrophotometer, 8-hydroxy-2-deoxyguanosine was analysed by sandwich ELISA, Glutathione peroxidase and Superoxide dismutase were analysed by spectrophotometer and 8-Isoprostane was estimated by ELISA. Results: The present study included a total of 92 patients clinically diagnosed with oral submucosal fibrosis. It is seen that out of 92 patients, 53 were males and 39 were females accounting for 57.6% and 42.39% respectively. The mean age in years in males and females were 28.97±5.80 and 32.39±3.77 years respectively. The mean levels of oxidative stress markers were significantly increased and antioxidant levels were significantly decreased as OSMF advances. Pairwise comparison of mean values of salivary oxidative stress and antioxidant biomarkers were performed using post hoc analysis by Tukey test. Table 4 displays an almost highly significant (P<0.001) difference between the mean values of all the salivary biomarkers when compared pairwise. However, a significant difference (P=0.001) was found between Grade 2 vs Grade 3 for 8-Isoprostane. The mean difference between pair Grade 3 vs Grade 4 was found to be not significant for salivary Glutathione Peroxidise and salivary 8- isoprostane having P values of 0.52 and 0.41, respectively. Conclusion: The results of our study showed that the concentration of MDA, isoprostane, 8- Hydroxydeoxy-guanosine levels were increased significantly as the clinical stage and histopathological grade of OSMF advances suggesting these biomarkers can be used as a reliable biochemical marker and also a prognostic marker to assess the extent of oxidative damage in OSMF. The concentration of antioxidant enzymes showed progressive decline as OSMF advances, indicating the potential role of supplementation of antioxidants in these patients to decrease the progression of the disease. [ABSTRACT FROM AUTHOR]