Human tissues containing melanocytes secreting melanin pigments contributes a low-level protection of the skin and hair follicles against many factors, but in oral mucosa, the melanin levels and functions vary with a microbial environment which is an unknown mechanism and its role is still not fully understood, especially defense against the oral pathogens in the mucosa. This study addresses a possible role of melanin has a multifunctional activity to protect the gingiva during child to adult age by exploring, the mechanism of interaction with oral bacteria, fungus, biofilm-forming bacteria and inflammatory cox-2 proteins using in-silico analysis. Our results showed, human oral mucosa containing melanin act as a antagonist against DHPS containing E.coli and S.aureus (antibacterial), ScNMT in S.cerevisae (antifungal), quorum sensing P.aeruginosa containing LasA (antibiofilm property), except human COX-2 not showed an anti-inflammatory activity and the binding energies for melanin with DHPS of E.coli and S.aureus (-8.9 and -7.1 kcal/mol) respectively, melanin with ScNMT (-8.0 kcal/mol), P.aeruginosa (LasA) (-8.3 kcal/mol) and Cycloxygenase-2 with melanin (-10.3 kcal/mol). We explored the importance of oral mucosa containing melanin with broad-spectrum activity against oral pathogen with no anti-inflammatory activity based on the route of transmission, the oral pathogens select for their survival in the gingiva and tooth during the different stage ages of humans.