On the basis of previous research on osthole, twenty-four ester derivatives were designed and synthesized, and confirmed by ₁^H NMR, ₁₃^C NMR and elemental analysis. The result showed that the activities of compound 4h and 4t against S. aureus, MRSA, E. coli and FREC were the most significant, the MIC of 4h was 4, 16, 8, 16 μg/mL respectively, and the MIC of 4t was 2, 8, 4, 8 μg/mL respectively, and their inhibitory activities against the tested bacteria were better than that of previous compounds, which have potential research value.