One of the most frequent congenital orofacial defects is the cleft lip and palate. Local tissue defense factors are known to be important in immune response and inflammatory and healing processes in the cleft tissue; however, they have only been researched in older children during mixed dentition. Thus, the aim of this study is to assess the distribution of LL-37, CD-163, IL-10, HBD-2, HBD-3, and HBD-4 in children before and during milk dentition. The unique and rare material of palate tissue was obtained from 13 patients during veloplastic surgeries during the time span of 20 years. Immunohistochemistry, light microscopy, semi-quantitative evaluation, and non-parametric statistical analysis were used. A significant decrease in HBD-3 and HBD-4 in the connective tissue was found, as well as several mutual statistically significant and strong correlations between HBD-2, HBD-3, HBD-4, and LL-37. Deficiency of HBD-3 and HBD-4 suggests promotion of chronic inflammation. The scarcity of HBD-4 could be connected to the different signaling pathways of dental pulp cells. Mutual correlations imply changes in the epithelial barrier, amplified healing efficiency, and increased antibacterial line of defense. Deprivation of changes in IL-10 quantity points to possible suppression of the factor. The presence of similar CD-163 immunoreactive substances produced by M2 macrophages was also observed.