Two series of novel fraxinellone-based thioethers containing 1,3,4-oxadiazole moiety were prepared as insecticidal agents against the oriental armyworm, Mythimna separata Walker. The structural assignment was based on the spectroscopic and X-ray analysis data. Among all the target compounds, compounds 4b, 4k, 5b, 5j and 5k exhibited more potent insecticidal activity with final mortality rates (FMRs) of > 65%, especially 4k with the FMR of 75.9%, when compared with toosendanin. Some interesting results of structure–activity relationships were also discussed.