Antibiotic resistance has become one of the most urgently important problems facing healthcare providers. A novel series of dipicolylamine-containing carbazole amphiphiles with strong Zn<sup>2+</sup> chelating ability were synthesized, biomimicking cationic antimicrobial peptides. Effective broad-spectrum <b>16</b> combined with 12.5 μg/mL Zn<sup>2+</sup> was identified as the most promising antimicrobial candidate. <b>16</b> combined with 12.5 μg/mL Zn<sup>2+</sup> exhibited excellent antimicrobial activity against both Gram-positive and Gram-negative bacteria (MICs = 0.78-3.125 μg/mL), weak hemolytic activity, and low cytotoxicity. Time-kill kinetics and mechanism studies revealed <b>16</b> combined with 12.5 μg/mL Zn<sup>2+</sup> had rapid bacterial killing properties, as evidenced by disruption of the integrity of bacterial cell membranes, effectively preventing bacterial resistance development. Importantly, <b>16</b> combined with 12.5 μg/mL Zn<sup>2+</sup> showed excellent <i>in vivo</i> efficacy in a murine keratitis model caused by <i>Staphylococcus aureus</i> ATCC29213 or <i>Pseudomonas aeruginosa</i> ATCC9027. Therefore, <b>16</b> combined with 12.5 μg/mL Zn<sup>2+</sup> could be a promising candidate for treating bacterial infections.