ABSTRACT The Microbial Desalination Cell (MDC) stands out as an innovative and a sustainable technology for both renewable energy generation and water treatment. The choice of electron acceptor significantly influences the efficiency of electricity flow. This study focuses on exploring the MDC performance under different conditions, including variations in cathode electron acceptors, initial pH levels, and hydraulic retention time (HRT). The investigation assesses simultaneous reduction of TDS and power generation from Caspian Sea water, a prominent saline water source in northern Iran, in both open-circuit (OC) and closed-circuit (CC) modes. The findings reveal that sodium hypochlorite, potassium permanganate, and potassium bromate as catholyte achieved TDS reduction rates of 84%, 77%, and 72%, respectively, under CC conditions at pH 5. Furthermore, it was observed that increasing HRT and pH levels lead to a decrease in desalination efficiency and power generation. Notably, the study highlights that the maximum power density was attained using permanganate, hypochlorite, and bromate as catholyte in both OC and CC configurations. By showcasing the adaptability of MDC performance with different cathode electron acceptors under varying conditions, this research offers valuable insights for optimizing MDC efficiency when treating real saline water sources.