At present, the control of membrane biofouling is mainly achieved by regulating quorum sensing. In this study, the quorum-sensing inhibitor astragaloside IV was used to prevent membrane biofouling in a membrane bioreactor. It was found that astragaloside IV at a concentration of 1 mg/L doubled the time taken for membrane contamination to occur, and decreased the energy required for filtration by 62% without affecting reactor’s processing performance. This is because the addition of astragaloside IV decreased the soluble microbial protein concentration and the loosely bound extracellular polysaccharide content. Biodiversity analysis indicated that astragaloside IV may have inhibited membrane contamination by interfering with the structure of the bacteria community, particularly the populations of quorum-sensing bacteria, bacteria related to extracellular polymeric substance production, and quorum-quenching bacteria. This is the first time the effects of astragaloside IV on membrane contamination in membrane reactors and the inhibition mechanisms involved were investigated. Using astragaloside IV could effectively decrease the energy consumed in operating a membrane bioreactor.