In this study, a series of anionic polyelectrolytes, sodium carboxymethyl dextrans with different molecular weights (CM-dextran-1000/5000/20,000), are facilely prepared via a one-step reaction and applied as novel draw solutes in forward osmosis (FO) process. Various characterizations (FTIR, NMR, conductivity titration and cytotoxicity test) are performed to investigate the chemical structure, degree of substitution (DS) and toxicity of synthesized CM-dextrans. Effects of the solution concentration and solute molecular weight on physicochemical properties (relative viscosity, conductivity and osmotic pressure) of CM-dextran draw solutions as well as their corresponding FO performances are investigated systematically. In comparison with FO performance of 1 M NaCl draw solution (water flux of 22.1 LMH; reverse solute flux of 9.8 gMH), 40 wt% CM-dextran-1000 draw solution shows a higher water flux (24.9 LMH) and a much lower reverse solute flux (0.97 gMH) in PRO mode. Furthermore, CM-dextran solution with the low reverse solute diffusion, nontoxicity, and the high osmotic pressure, can be potentially used as draw solution for desalination and protein enrichment via FO. The theoretical calculation also confirms that FO process shows lower special energy consumption than OF process in the application of protein concentration. (C) 2019 Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.