Following access into cell, colloidal silver nanoparticles exhibit generalized cytotoxic properties, thus appear as omnipotent microbicidal, but not suitable for systemic use unless are free of toxic effects on host cells. The serum capped silver nanoparticles when prepared from silver nitrate, using dextrose as reducing and group-matched homologous serum as a stabilizing agent, selective endocytosis and oxidative stress dependent bio-functional damages to the host are mostly eliminated. For their bio-mimicking outer coat, there is least possibility of internalization into host-cells or liberation of excess oxidants in circulation following interaction with erythrocytes or vascμμμar endothelial cells. Presence of infection specific antibody in the serum can make such nano-conjugates more selective. A potent antimicrobial action and a wide margin of safety for mammalian cells in comparison with very similar PVA-capped silver nanoparticles have been demonstrated by in-vitro challenge of such nanoparticles on different microbes, human liver cell-line, and in-vivo study on mice model. This may open-up wide-range therapeutic prospects of colloidal nanoparticles.