Abstract Polyoxometalates (POMs), green materials with extraordinary structure and physicochemical properties, have interesting pharmacological properties. In this work, phosphomolybdic acid–reduced graphene oxide (PMo–RGO) nanocomposite was prepared by a simple hydrothermal reduction method without using any toxic material. For the first time, the antibacterial properties of PMo and PMo-RGO were evaluated against E. coli by microdilution and colony counting methods. We studied both influence of reagents concentration and encountering time on antibacterial activity. Since both MIC and MBC values for pure PMo are 3920 μg/ml, it acts as a bacteriocidal agent. After entrapping PMo on graphene, this concentration reduced to 512 μg/ml due to its subnanometer size and increased specific surface area leading to enhance antibacterial reactivity. The growth curves of PMo-RGO were fitted well with a Gaussian Equation. The slopes of growth phase against PMo-RGO concentrations were plotted and fitted with a quadratic equation.