To address the antibiotic resistance crisis, this study developed a novel antibiotic synergy strategy by constructing charge-transfer complexes of ofloxacin/sulfamerazine with three natural organic acids. Experiments demonstrated that the complexes significantly enhanced antibacterial activity against Escherichia coli and Staphylococcus aureus (increased inhibition zones, decreased MIC). Mechanistic studies revealed that the complexation achieved synergistic enhancement by optimizing antibiotic charge states, improving surface morphology, and enhancing membrane permeability, providing new insights for antimicrobial agent development.