Background: Early childhood caries (ECC) has many etiologies such as families’ socioeconomic status, parents’ education and awareness, prolonged and improper bottle or breastfeeding, consuming sweet foods and high-sugar diets, brushing techniques, immaturity of children’s immune system, family size, and Streptococcus mutans. 
Evidence Acquisition: The data used in our review were searched from articles published between 1950 to 2021 and using ECC, children, saliva, salivary biomarkers, salivary enzymes, salivary peptides, salivary proteins, and immunity as keywords, collected from official web pages (Scopus, PubMed, Embase, and Google scholar) and documents published from different international institutions. The search was limited to articles published in the English language. After screening the abstract, the full text of 194 related studies was reviewed. Finally, 78 most related studies were selected.
Results and Conclusion: ECC-related salivary proteins and peptides are proline-rich proteins, salivary mucins, lactoferrin, immunoglobulins, toll-like receptors, lysozyme, histatins, statherin, defensins, calprotectin, and cytokines. ECC-related enzymes are amylase, lysozyme, lactoperoxidase, alkaline phosphatase, carbonic anhydrase VI, lactate dehydrogenase, and glucosyltransferase B. Immunity factors affecting ECC include IgA (sIgA), IgG, IgM, salivary mucins, lactoferrin, TLRs, histatins, statins, defensins, calprotectin, lysozyme, lactoperoxidase, cytokines and interleukins, cathelicidin (LL-37), agglutinin, cysteine, and neutrophils.