Increased seawater temperature leads to harmful algal blooms (HABs), which releases toxic materials and extracellular polymeric substances (EPS) that are harmful to both humans and the environment. Reverse osmosis (RO) with cartridge filter (CF) as the pretreatment process is often used for desalination process. However, the EPS causes severe fouling on the CF, and RO membrane. Disinfectants, such as NaOCl and ClO2, are commonly used to remove biofouling, because they can oxidize and kill microorganisms. Therefore, our study aims to utilize NaOCl and ClO2 during the CF-RO process to minimize the algal growth within the system and minimize the fouling induced by EPS. Results from this study show that CF can remove more than 50% of protein and 14% of polysaccharides but is not effective in removing toxins. However, with disinfectants, toxic materials were completely oxidized. Improved removal of EPS with CF improved overall performance. The flux reduction in RO process without disinfection was over 60%, however, the flux decline was about 44% and 10% with NaOCl and ClO2, respectively. Both disinfectants were found to be effective, however use of ClO2 is recommended because it is less damaging the membrane, yet more effective in enhancing the performance.