Background: Resistance or susceptibility to caries is significantly correlated with the alterations in salivary proteins and cytokines, a useful biomarker in predicting caries’ risk and prognosis. Bacteria colonize the oral cavity and lead to inflammation, which induces both innate and adaptive immune responses by the host. A predominant cell of inflammation like T lymphocytes, monocytes, macrophages, and endothelial cells expresses many pro-inflammatory cytokines. Interleukin-6 (IL-6) is a multifunctional cytokine transiently produced in response to tissue injury and infections, thus correlating with the extent of inflammation and edema in the pulp. Studies have revealed a correlation between IL-6 levels and different pulpal conditions, which can contribute to the early diagnosis of pulpal inflammation in caries exposures. Aim and objective: To assess and compare the salivary IL-6 levels in patients before and after caries removal. Materials and methods: A total of 20 patients have participated in this study based on inclusion criteria. A pretreatment saliva (first) sample was collected, centrifuged, and stored at −80°C. Based on the clinical examination and investigations, the treatment plan was formulated for each patient. After oral prophylaxis and restorative treatment, the patients were followed up after 45 days. The posttreatment (second) saliva samples were collected, and both the samples (first and second) were subjected to the ELISA test to measure the IL-6 levels. Results: The obtained optical density values were statistically analyzed using the Wilcoxon signed-rank test. As estimated in this study, the mean salivary IL-6 level was 15.32 ± 17.54, which reduced to 4.19 ± 1.45 after 45 days or one and half months of treatment. Conclusion: The levels of IL-6 reduced significantly after the complete removal of caries and restoring those teeth with restorative materials showing that there exists a strong correlation between the two. Clinical significance: A strong correlation is present between the IL-6 level and the extent and severity of the carious lesions. Posttreatment, there is a significant reduction of the IL-6 values, which can be attributed to the complete removal of dental caries.