To capture and kill bacteria cells, many antimicrobial agents contain cationic groups that take advantage of the high binding affinity for negatively charged bacterial cells. However, the use of quaternary ammonium compounds usually causes serious bacterial resistance. Guanidine derivatives, which are nontoxic and highly soluble in water, are considered as a broad-spectrum antimicrobial agent. Bin Wang et al. on on page 3489 design and synthesize a novel modified guanidine-based oligomer that can enhance the antimicrobial activity and extend the antimicrobial spectrum. When Escherichia coli is treated with the modified guanidine oligomer, as shown in the cover image, the height of bacterial cells is reduced, the surface becomes rough, the membrane is severely damaged, and most of the intracellular components are leaked.