Plant extracts are a cost effective, ecologically friendly, and efficient alternative for the large scale synthesis of nanoparticles. In the present study, green synthesis of silver nanoparticles (Ag NPs) by using Calophyllum inophyllum L. leaf extract was evaluated. The Ag NPs were characterized by Scanning Electron Microscopy (SEM), UV–Visible absorption spectroscopy and FT–IR analysis. The SEM analysis of silver nanoparticles revealed spherical shape in morphology with their sizes ranging from 70 to 100 nm. The in vitro antimicrobial activity of the Ag NPs synthesized by C. inophyllum leaf extract was studied against some human pathogenic microbes by using agar well diffusion assay. The synthesized Ag NPs exhibited good antimicrobial potential against tested bacterial and fungal pathogens. This plant leaf extract compounds can be extended to the synthesis of other metal and metal oxide nanoparticles.