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[Display omitted] • Novel ferulic acid derivatives with oxadiazole were designed and synthesized. • The synthesized compounds showed significantly antiviral activity. • Compound 6 h can intensify the activities of some defensive enzymes. • 6 h regulates phenylpropanoid biosynthesis pathway and chloroplast function. • Some of the synthesized compounds could be used as potential elicitors. A series of new ferulic acid derivatives bearing an oxadiazole ether was synthesized by introducing a structure of oxadiazole into trans -ferulic acid via an ether linkage. The synthesized target compounds were evaluated in vivo for their anti-TMV (tobacco mosaic virus) activity, which indicated that some synthesized compounds displayed strong activity for controlling TMV. For protective activity, compounds 6f and 6 h had the most activities of 65% and 69.8% at 500 mg L-1, respectively. Compounds 6a , 6b , 6e , 6f and 6 h showed > 60% curative activities at 500 mg L-1. Preliminary proteomics analysis showed that compound 6 h could regulate the phenylpropanoid biosynthesis pathway and chloroplast function. These results indicated that synthesized novel ferulic acid derivatives could be used for controlling TMV. [ABSTRACT FROM AUTHOR]