Display omitted •Thirty novel (+)- nootkatone derivatives were prepared by molecular hybridization.•Compounds B9 and B21 displayed more potent insecticidal activities than azadirachtin.•B9 and B21 also showed low cytotoxic activities on normal mammalian cells.•Inhibition of acetylcholinesterase may be the mode of insecticidal action of B9. (+)-Nootkatone, a non-food bioactive natural bicyclic sesquiterpene ketone, is isolated from Chamaecyparis nootkatensis D. Don Spach as a renewable forest resource. In continuation of our effort to develop synthetic natural derived insecticides from non-food bioactive products, a small library of thirty N-(1,3- thiazol-2-yl)carboxamides fused (+)-nootkatone was prepared by molecular hybridization and characterized by 1H/13C NMR, HR-MS, and IR spectroscopy. Their insecticidal activities against Mythimna separata Walker and Plutella xylostella Linnaeus were evaluated. Compounds B6, B7, B9, B19–21 and B24 showed better insecticidal activity against M. separata than the botanical insecticide azadirachtin, and their LC50 values ranged from 0.55−0.68 mg/mL. Particularly, compound B9 exhibited 1.87-fold more pronounced insecticidal activity against M. separata than azadirachtin. The insecticidal activity of B21 against P. xylostella was 1.37-fold of that of azadirachtin. Through acetylcholinesterase (AChE) inhibitory activity and molecular docking studies, AChE may be the insecticidal target of B9 against M. separata. In addition, three pronounced compounds B9, B21 and B24 exhibited low hemolytic and cytotoxic activities on normal mammalian cells. These findings will give insights into the further development of (+)-nootkatone derivatives as potentially synthetic natural derived insecticides for pest management.