Background: Scientific clue of awareness, perceptivity to dental caries in the population with Down’s syndrome is hampered and adverse, making it challenging to establish firm conclusions. Wide range of developmental delays and physical disabilities caused by a genetic disease, Down’s syndrome, which is caused when abnormal cell division results in extra genetic material from chromosome 21. This disease has an incidence of 1 in 600-700 live births. One of the most prominent oral manifestations of Down’s syndrome is low incidence of dental caries. Diminished salivary pH and bicarbonate levels. Biochemical alterations in saliva, delayed eruption, less susceptibility to cariogenic environment, shallow fissures of teeth, all contribute to the lower risk of dental caries. Aim: To compare the glycoproteins, proline rich proteins in children with Down’s syndrome and in caries free children. Settings and Design: The study was conducted in 5-18 years old 30 children comprising two groups Group-1: 15 children with Down’s syndrome, Group-2: 15 caries free healthy children. Materials and Methods: Glycoproteins, proline rich proteins by SDS-PAGE were compared among both the groups. Statistical Analysis: Unpaired t-test, chi-square test was used to compare the data between the study and control group. Results: The out cropping shows no statistical difference in the number of PRP bands in either of the groups. Conclusion: The present study results highlight the central axial dominant role played by PRP’s might be the reason in the protection against dental caries and further detection by monoclonal antibody or LC/MS analysis and other assays to support the result at nano level which escort to burnish the potentiality of its use in caries prediction.