Background: Oral potentially malignant disorders (OPMDs) represent a spectrum of mucosal conditions with an increased risk of malignant transformation. Although tobacco and alcohol remain established etiological factors, the role of restorative dental materials in contributing to mucosal changes has gained interest due to their chemical composition, degradation by-products, and chronic intraoral exposure. Objective: To evaluate the association between OPMDs and the use of different restorative dental materials among adult patients. Methods: A cross-sectional study was conducted on adult patients attending dental outpatient clinics. Detailed oral examinations were performed to diagnose OPMDs following WHO criteria. History of dental restorations, including amalgam, composite resin, glass ionomer cement (GIC), ceramic and metal-ceramic restorations, was recorded. Demographic variables, habits, and duration of restorations were included. Statistical analysis involved chi-square tests and logistic regression to determine associations. Results: Patients with metal-based restorations (amalgam and metal-ceramic crowns) showed a higher prevalence of OPMDs compared to those with tooth-colored materials. Composite resins demonstrated minimal association overall, whereas GIC restorations showed no significant relationship. Logistic regression indicated that presence of ≥3 metal restorations increased the odds of OPMDs after adjusting for tobacco habits (p < 0.05). No association was found between ceramic restorations and OPMDs. Conclusion: A significant association was observed between OPMDs and multiple metal-based restorations, possibly due to galvanic reactions, corrosion by-products, and chronic mucosal contact.