Introduction: Salivary matrix metalloproteinase-9 (MMP-9) is an established diagnostic biomarker for detection and prognosis of oral cancer. Objectives: The current study aimed to estimate salivary MMP-9 in oral leukoplakia and oral submucous fibrosis (OSMF), which are considered as oral potentially malignant disorders (OPMDs). Material and methods: A comparative observational study of 60 subjects was conducted, including 20 patients diagnosed with OSMF (group A, n = 20), 20 diagnosed with oral leukoplakia (group B, n = 20), and 20 as healthy controls (group C, n = 20) according to standard criteria. Unstimulated salivary samples were collected for evaluation of MMP-9 by enzyme-linked immunosorbent assay (ELISA). One-way analysis of variance (ANOVA) test was applied for comparison of groups. Bonferroni-adjusted one-way ANOVA test was performed for intra-group comparison. Results: Descriptive statistics of the data revealed that mean age of study participants in group A, group B, and group C were 50.30 ± 9.96 years, 46.70 ± 12.59 years, and 33.30 ± 4.70 years, respectively. Mean salivary MMP-9 level in OSMF, oral leukoplakia, and control group were 9.42 ng/ml, 10.59 ng/ml, and 2.96 ng/ml, respectively, with a p-value < 0.001 between OSMF and oral leukoplakia when compared with controls. Conclusions: A significant difference was noted in salivary MMP-9 levels among patients with OPMD's compared to controls. A slightly higher value of MMP-9 was observed in oral leukoplakia. Estimation of salivary MMP-9 level is a non-invasive and a reliable biomarker in diagnosis of OPMD's and in accessing their malignant transformation.