The antibacterial system based on the silver element has been a very promising antibacterial material. However, the antibacterial activity of silver nanomaterials largely depends on their chemical composition and physical properties. Herein, we prepared ultrasmall silver nanoclusters by directly reducing silver ions with antimicrobial peptide in a green way. The positively charged peptide ligands drove the silver nanoclusters binding to bacteria by electrostatic attraction. Contrary to the large-sized silver nanomaterials, the ultrasmall silver nanoclusters were able to rapidly penetrate bacteria membranes via strong hydrophobic association, significantly promoting the generation of reactive oxygen species, and the subsequent high oxidative stress led to bacterial death. Moreover, the silver nanoclusters with antibacterial peptide ligand exhibited good stability, low cytotoxicity, and long-term antibacterial activity. Besides, synergistic enhancement of silver nanoclusters on antibacterial activity was observed. Therefore, the silver nanoclusters conjugated with the antimicrobial peptide can act as a synergistic antibacterial agent, in which their bio-interactions with bacteria have been regulated to achieve a rapid, long-lasting, and broad-spectrum antibacterial effect.