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Background: Recently, a continuous growth of interest has been observed in antimicrobial peptides (AMPs) in the light of an alarming increase in resistance of bacteria and fungi against antibiotics. AMPs are used as biomarkers in diagnosis and monitoring of oral cavity pathologies. Therefore, the determination of specific protein profiles in children diagnosed with early childhood caries (ECC) might be a basis for effective screening tests and specialized examinations which may enable progression of disease. Methods: The objective of the studies was to determine the role of histatin-5 and $\beta$-defensing-2 as a diagnostic marker of early childhood caries progression. In this work, results of concentration determination of two salivary proteins (histatin-5 and $\beta$-defensin-2) were presented. In addition, bacterial profiles from dental plaque in various stages of ECC and control were marked. The assessment of alteration in the concentration of these two proteins in a study group of children with various stages of ECC and a control group consisting of children with no symptoms was performed by enzyme-linked immunosorbent assays. Results: The statistical analysis showed a significant increase in the concentration of histatin-5 and $\beta$-defensin-2 in the study group compared to the control group and correlated with the progression of the disease. Conclusions: The confirmation of concentration changes in these proteins during the progression of dental caries may discover valuable disease progression biomarkers.