• Saliva substitutes containing Lysozyme or Lactoferrin had antibacterial effects on Streptococcus mutans. • Samples treated with both between 2.5–100 μg/ mL LF and 5–200 μg/ mL LYZ were found to have significant wound healing effects. • A statistically significant difference in bacterial adhesion was observed between study groups (saliva substitute, saliva substitutes containing Lysozyme or Lactoferrin) and human saliva groups. • Bacterial adhesion was observed significantly higher in human saliva group than the study groups. • The amount of adhered Streptococcus mutans was significantly higher in saliva substitute group compared to saliva substitute containing Lysozyme and saliva substitute containing Lactoferrin groups. However, no statistically significant relationship was obtained between saliva substitute containing Lysozyme and saliva substitute containing Lactoferrin groups. To determine the antibacterial effects of different saliva-substitutes-containing-lysozyme(LYZ) or-lactoferrin(LF) on Streptococcus mutans (S. mutans) in comparison with human saliva. In vitro wound-healing assay was performed with L929 mouse fibroblast cell line by using various concentrations 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). 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 μg/mL LF and 5−200 μg/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). 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. [ABSTRACT FROM AUTHOR]