A series of hybridized pyrrolidine compounds with a 1,2,4‐oxadiazole moiety were synthesized to develop effective molecules against the enzymes DNA gyrase and topoisomerase IV (Topo IV). Compounds 8–20 were developed based on a previously disclosed series of compounds from our lab, but with small structural modifications in the hopes of increasing the compounds' biological activity. In comparison to novobiocin, with IC₅₀ = 170 nM, the findings of the DNA gyrase inhibitory assay revealed that compounds 16 and 17 were the most potent of all synthesized derivatives, with IC₅₀ values of 180 and 210 nM, respectively. Compound 17 had the strongest inhibitory effect against Escherichia coli Topo IV of all the synthesized compounds, with an IC₅₀ value of 13 µM, which was comparable to novobiocin (IC₅₀ = 11 µM). Therefore, hybrids 16 and 17 appeared to be potential dual‐target inhibitors. In the …