In this study, the antibacterial activity of the stems and leaves of Astragalus membranaceus (denoted as AMSL herein) was explored through testing the inhibition zone diameter and the minimum inhibitory concentration (MIC) of different components on six test bacteria by the filter paper method and double dilution method respectively. Besides, the antibacterial mechanism of AMSL was preliminarily described by measuring the growth curve of Escherichia coli and evaluating the influence of AMSL on the release of macromolecular substances in the suspension. The results showed that the total saponins of AMSL had obvious antibacterial activities against the six test bacteria, especially its effect on Escherichia coli with the MIC value of 12.5 μg/mL. The total flavonoids had significant antibacterial activities against only two test bacteria with the MIC values of 93.8 μg/mL, and the total polysaccharides had no activity. After the extract of AMSL saponins was added to the bacterial suspension, the growth of Escherichia coli was severely inhibited and the content of macromolecules such as nucleic acids in the bacterial suspension increased, indicating that the AMSL exerted bacteriostatic action mainly by destroying the integrity of the cell membrane which caused the macromolecular substances to overflow. This study provides a theoretical basis for the application of AMSL as a natural preservative in the field of food preservation and storage.