Abstract <p>In this study, a series of novel vanillic acid derivatives incorporating 1,3,4-oxadiazole and thioether moieties were synthesized and their structures were confirmed using ¹H NMR, ¹³C NMR, and HRMS techniques. The results of bioactivity determination demonstrated that the target compounds exhibited moderate to good in vitro antibacterial activities against <i>Xanthomonas axonopodis</i> pv. <i>citri</i> (<i>Xac</i>) and <i>Xanthomonas oryzae</i> pv. <i>oryzae</i> (<i>Xoo</i>). Particularly, compound 2-{4-[(4-chlorobenzyl)oxy]-3-methoxyphenyl}-5-(propylthio)-1,3,4-oxadiazole displayed remarkable antibacterial activities against <i>Xac</i> and <i>Xoo</i> with EC₅₀ values of 5.58 and 18.82 μg/mL respectively, surpassing those of bismerthiazol and thiodiazole copper. To the best of our knowledge, this study presents the first report on the synthesis and antibacterial activity evaluation of vanillic acid derivatives incorporating 1,3,4-oxadiazole and thioether moieties.</p>