Abstract
Oral leukoplakia (OL) is a common oral potentially malignant disorder in which chronic inflammation and carcinogenic exposures may promote oxidative stress. Saliva is in direct contact with the lesion and represents a non-invasive medium for assessing redox dysregulation. This systematic review and meta-analysis synthesized evidence on salivary oxidative damage markers and antioxidant defenses in OL compared with healthy controls. A PROSPERO-registered systematic review (CRD420251242238) was conducted in accordance with PRISMA and Cochrane guidelines. PubMed, Scopus and Web of Science were searched up to 10 December 2025 for observational studies comparing salivary oxidative stress and/or antioxidant markers in patients with clinically and/or histopathologically confirmed OL and healthy controls. Case-control and cross-sectional studies reporting quantitative data were included. Risk of bias was assessed using a modified Newcastle-Ottawa Scale. When ≥2 datasets were available, standardized mean differences (SMDs) with 95% confidence intervals (CI) were pooled. Meta-analysis showed significantly higher salivary malondialdehyde in OL (SMD = 1.47; 95% CI: 0.55-2.39), indicating enhanced lipid peroxidation. OL was also associated with significantly lower levels of reduced glutathione, vitamins C and E, and uric acid. For 8-hydroxy-2'-deoxyguanosine, a non-significant trend towards higher levels was observed with substantial heterogeneity. Evidence for TBARS, total antioxidant capacity and enzymatic antioxidants was limited. OL is associated with a salivary redox imbalance favoring a pro-oxidant state. High heterogeneity and limited biomarker-specific evidence highlight the need for larger, standardized prospective studies to validate salivary redox markers for OL monitoring and risk stratification.