<p>This study aimed to investigate the performance of large-molecular-weight single and mixed draw solutes in the forward osmosis process for brackish water desalination. Magnesium sulfate and sucrose solutions with osmotic pressures of 14, 28, and 42 bar were employed as draw solutes, while deionized water and synthetic brackish water containing 10,000 ppm NaCl were used as feed solutions. The performance of the draw solutes was systematically evaluated in terms of water flux, water recovery, and specific energy consumption in the forward osmosis process, as well as their regeneration using nanofiltration. Although higher osmotic pressure typically enhances permeate flux, an osmotic pressure of 28 bar was found to be optimal for desalinating high-salinity brackish water using these solutes. At higher concentrations, increased solution density and reduced solute diffusivity intensified internal concentration polarization, resulting in a decline in water flux. Furthermore, a comparison between the hybrid forward osmosis–nanofiltration system and a reverse osmosis process was conducted with respect to specific energy consumption and product-water quality. Minimum specific energy consumption values of 2.95 and 1.32 kWh·m⁻³ were estimated for brackish water desalination using the hybrid forward osmosis–nanofiltration system and the stand-alone reverse osmosis process, respectively. The findings indicate that although the hybrid system can be improved through optimization of feed and draw solute properties, it cannot surpass the performance of commercial reverse osmosis for treating high-salinity waters.</p>