Due to the lack of affordable and feasible wastewater treatment technologies, various industries in developing countries are discharging chromium (Cr) without meeting the environmental standards. Here, the aim was to employ forward osmosis (FO) using aquaporins (AQP)-based biomimetic membranes and optimize the Cr rejection through response surface methodology (RSM). The initial concentration of draw solution, feed solution, and time was selected as independent variables in order to optimize Cr rejection and water flux. A high Cr rejection efficiency and water flux were achieved under the optimal conditions. These results revealed that the FO process applying an AQP membrane beside the RSM could be considered to treat wastewaters containing heavy metals.