Objective: To determine the antibacterial effects of different saliva-substitutes-containing-lysozyme(LYZ) or-lac-toferrin(LF) on Streptococcus mutans(S. mutans) in comparison with human saliva. Design: In vitro wound-healing assay was performed with L929 mouse fibroblast cell line by using various con-centrations of LYZ and LF to determine optimum concentrations and to confirm do not show any cytotoxicity of proteins according to cell culture studies. Antibacterial effect was assessed by determining Minimum Inhibitory Concentrations for all groups on S.mutans. Bacterial adhesion of S. mutans for 4 h on hydroxyapatite(HAP) discs after application of different saliva substitutes was evaluated. The formulations were:saliva-substitute(Group SS); saliva-substitute-containing-Lactoferrin(Group SSLF);saliva-substitute-containing-Lysozyme(Group SSLYZ). Human saliva was control group(Group HS). Results: In vitro wound healing assay results showed that, when added into the cell culture media, LYZ and LF significantly increase 48-h scratch wound closure compared to the cell culture media(p < 0.0001). At the end of second day, samples treated with both between 2.5-100 mu g/mL LF and 5-200 mu g/mL LYZ were found to have significant wound healing effect(p < 001). It was observed that saliva-substitutes-containing-LYZ or-LF had antibacterial effects on S.mutans. Bacterial adhesion on HAP discs was observed significantly higher in control group than in study groups. The amount of adhered S. mutans was significantly higher in Group SS than other study groups(p < 0.0001). However, no statistically significant difference was found between the number of bacteria adhered to HAP discs between SSLYZ and SSLF groups(p > 0.05). Conclusions: The study of cell viability and wound healing was great significance in the optimum concentrations of LYZ and LF. Among formulations, saliva-substitutes-containing-LYZ or-LF exhibited higher inhibitory effect on S.mutans.