In the present study, surface functionalized mannan sulphate silver nanoparticles (MS-AgNPs) were prepared and assessed for their wound healing potential. 20nm sized, spherical MS-AgNPs were prepared by one pot synthesis approach wherein the sulphated polysaccharide mannan sulphate (MS) played dual role of reducing as well as capping agent. The crystalline MS-AgNPs exhibited surface plasmon resonance centered at 400nm along with −32.40mV zeta potential. These stable MS-AgNPs showed enhanced cytocompatibility, targeting potential and cellular uptake in murine macrophages, human skin fibroblasts and human keratinocytes as compared to citrate reduced silver nanoparticles (C-AgNPs). In the in vivo excision and incision wound models, MS-AgNPs as hydrogel formulations indicated better efficacy than the conventional and marketed silver formulations. Thus, the synthesized MS-AgNPs depicted a promising potential for site-specific topical delivery in accelerated wound therapy.