Background: Early childhood caries is a major oral health problem in most industrialized countries, affecting the overall quality of life of children. It is caused by the action of bacterial acids on the enamel surface thereby demineralizing it and progressively destroying the tooth. It presents initially as smooth-surface carious lesions affecting the primary maxillary incisors. With the advancement of the lesion, decay progresses further to involve other primary teeth as well and if not treated early, the caries may involve the pulp leading to irreversible pulpitis. Matrix metalloproteinases (MMPs) are a group of endopeptidases that degrade almost all the proteins of the extracellular matrix (ECM). Among the different types of MMP, MMP-9 (gelatinase B) is one of the chief MMPs responsible for the breakdown of the organic matrix. Traces of MMP-9 can be found in the human carious lesions, saliva, and gingival crevicular fluid. They are activated by the release of acids by cariogenic bacteria and once activated they are able to digest demineralized dentin matrix. Thus, host-derived MMPs, which are activated by bacterial acids have a crucial role in the destruction of dentine by caries. Thus, this study was undertaken to investigate the effect of 38% silver diamine fluoride (SDF) solution on MMP-9 levels. Aim: This clinical trial investigated the MMP-9 levels before and after the application of 38% SDF in children with early childhood caries. Materials and methods: About 15 children were selected and were subjected to clinical and radiographic assessment before the commencement of the procedure. After the collection of saliva, the teeth with carious lesions were isolated and SDF was applied. Saliva samples were again collected after 1, 3, and 6 months postapplication of SDF. The collected saliva samples were then analyzed for their MMP-9 levels using a human salivary enzyme-linked immunosorbent assay (ELISA) kit. Finally, the data obtained were subjected to statistical analysis by repeated measures of analysis of variance (ANOVA). Conclusion: The MMP-9 levels were found to be gradually increasing postapplication of 38% SDF and were significantly higher after 6 months and the highest mean difference in the MMP-9 levels was observed between baseline and 6th-month follow-up. Also, no new carious lesion appeared in the teeth during the experimental time period of 6 months and the decayed, extraction needed, filled teeth (deft) scores remained the same.