Introduction: Oral epithelial dysplasia, such as leukoplakia has a risk of malignant transformation. Curcumin, a natural polyphenol with anticancer properties, has been explored for many years as an alternative treatment for leukoplakia. Aim: To evaluate clinical and histopathological changes in oral leukoplakia from curcumin lozenges, this study compares pre- and post-medication effects. It is the first to involve general and oral pathologists from India and the USA, who independently assessed changes using WHO 2022 criteria. Material and Method: The study involved 10 patients and was conducted in three phases. Initial biopsy, and administration of curcumin lozenges (2 tablets thrice daily for 3 months) with clinical evaluation every month followed by a second biopsy. Results: Post-medication, clinically in a few cases reduction of lesion size was observed as a change from white to gray patches. Histopathological analysis was subjective and the three experts reported an overall improvement in architectural as well as cytological features suggesting the possible use of curcumin in treating cases of mild dysplasia. Conclusion: The pilot study suggests curcumin lozenges may benefit leukoplakia patients, but the small sample size limits definitive conclusions. Larger studies are needed to confirm these findings and assess long-term efficacy. WHO 2022 criteria showed subjectivity and variability. Despite this, they were useful for identifying specific changes. To the best of our knowledge to date, no other study has validated these WHO 2022 features in repeated biopsies.