In this study, real domestic wastewater treatment by forward osmosis-membrane distillation (FO-MD) integrated system was investigated in laboratory scale. The integrated membrane system presented a good separation performance and the removal efficiency of most contaminants in the domestic wastewater was higher than 90%. High molecular weight contaminants were completely removed, while a few low molecular weight contaminants permeated through the membrane. The FO membrane fouling layer mainly consisted of organic substances like polysaccharides and proteins, and was very loose and could be effectively removed by rinsing the membrane surface with tap water. By comparison, the MD membrane fouling was mainly induced by inorganic salts and was not as severe as that of the FO membrane. During 120 h continuous operation, the FO-MD integrated system exhibited satisfying performance stability and maintained a high water yield and high product water quality. The results indicated the potential of the FO-MD integrated system for municipal wastewater treatment in coastal cities, water purification and desalination.