The objective of this study is to assess the efficacy of topical Vitamin D derivative compared to topical retinoids in treating oral premalignant lesions, such as oral leukoplakia and oral lichen planus. The evaluation focused on the changes in clinical scores and salivary MMP-9 levels measured by ELISA. Results showed that 80% of cases in the Vitamin D derivative group and 70% of cases in the retinoids group were clinically improved after 4 weeks of therapy.There was a statistically significant difference in terms of the reduction in MMP-9 level before and after treatment with Vitamin D derivative more than retinoids, with a p-value of 0.01405. This investigation provides more evidence to support the idea that Vitamin D derivative may serve as a viable alternative to retinoids in the treatment of premalignant lesions depending on the significant impact of Vitamin D derivative in reducing salivary MMP-9 levels.