Background/introduction: Early childhood caries (ECC) is one of the most prevalent diseases in children worldwide. Early childhood caries is driven by a dysbiotic state of oral microorganisms, mainly caused by a sugar-rich diet. Additionally, poor oral hygiene or insufficient dental plaque removal leads to the rapid progression of ECC. Early childhood caries leads not only to dental destruction and pain in children but also affects the quality of life of the caregivers. Additionally, upon neutrophil activation at inflammatory locations, these proteases are externalized in an active state, aiding in the control of inflammatory and immunological responses. Any enzyme that catalyzes proteolysis reactions is known as a protease. Proteases are produced by human glands or derived from microbes in the oral cavity. Additionally, the oropharyngeal mucosae and crevicular fluids are sources of protease. Aim: This study is aimed at the estimation and correlation of salivary protease enzymatic activity in the saliva of children with and without ECC. Materials and methods: A total of 50 children were included in the study, which was divided into two groups: group I (caries-active) and group II (caries-free)—each consisting of 25 children. Unstimulated saliva samples were collected and subjected to a spectrophotometer for analysis. Salivary protease levels were estimated and correlated between caries-active and caries-free children. Results: The correlation between caries score and salivary protease activity was statistically significant with a moderate correlation. The comparison of mean salivary protease activity between caries-active and caries-free groups was statistically significant. However, the comparison of salivary protease activity based on different age-groups was not statistically significant, whereas gender and caries scores in group A were statistically significant. Conclusion: In conclusion, there is a substantial correlation between salivary protease enzyme levels and the severity of dental caries, and an increase in salivary protease enzyme levels is linked to a considerable rise in caries severity. As a result, prevention may be possible with early detection.