The use of nano-sized silver and its alloys represents an interesting alternative to common food preservation methods, which are based on radiation, heat treatment and low temperature storage. These metal nanoparticles, embedded within a polymeric matrix for instance, would extend the shelf life of perishable foods while acting as a bactericidal agent to prevent food-borne illnesses. Common methods used in the synthesis of metal nanoparticles require toxic solvents and reagents that could be harmful to health and the food itself. In addition, several steps are required to obtain aqueous stable, i.e. dispersible, silver nanoparticles. In this work we propose the microwave-assisted aqueous synthesis of silver-based nanoparticles, (Ag Based NP) functionalized by glutathione (GSH) in a single-step using sodium sulfite (Na2SO3), as reducing agent. Ag-Based nanoparticles were synthesized at pH 6 and 1:3:1 (AgNO3/GSH/ Na2SO3) molar ratio. UV-Vis measurement clearly showed the plasmon peak attributed to silver-based nanoparticles (374 nm). Highly monodispersed water stable Ag-based nanoparticles were observed and 3.897 ± 0.167 nm particle size was determined through Transmission Electron Microscopy. FT-IR measurements suggested the actual GSH-Ag based surface interaction through –SH and –COOH groups; the functionalization by GSH explained the high stability of the nanoparticles in aqueous suspensions. These Ag-GSH nanoparticles exhibited remarkable antimicrobial activity against E. Coli.