Tinospora cordifolia is one of the important medicinal plants, commonly referred as a rejuvenating herb. It has significant antimicrobial properties and that features found in stem, leaves, extract for microorganisms. T.cordifolia silver nanoparticles have significant antimicrobial activity, the alkaloids such as Berberine; present in the T.cordifolia herbal plant also gives the significant antimicrobial effects, which makes them a powerful source of antimicrobial agent. In the recent research findings, there are few topical gel formulations of AgNPs by green synthesis method and until now T.cordifolia silver nanoparticles incorporated in gel have not been formulated. Thus, the present research study aims to formulate and evaluate the Topical Nano silver gel of T.cordifolia (Guduchi) to minimize potential microbial infections. The green synthesis of silver nanoparticles was conducted by using T. cordifolia leaves and stem extract. The Preformulation studies were performed for the determination of presence of phytoconstituents such as alkaloids, flavonoids, glycosides etc. The characterization of T. cordifolia AgNPs was performed by UV spectroscopy studies, Percentage Entrapment efficiency, Fourier Transform Infrared Spectroscopy (FTIR). Particle size analysis; Zeta potential, SEM studies .The AgNPs of T. cordifolia and the extract was evaluated for Antimicrobial activity against Staphylococcus aureus& E. coli. The synthesized AgNPs of T. cordifolia was incorporated to gel base. That gel formulation evaluated for the physicochemical parameters such as pH, viscosity, spreadability, extrudability and also the antimicrobial activity against E. coli. The antimicrobial study of prepared Nano silver gel of T. cordifolia exhibited effective antimicrobial properties against E. coli. Hence; this study concluded that the formulated Nano silver gel of T. cordifolia can be used as an effective formulation for the treatment of antimicrobial infections.