AbstractBACKGROUNDPheromone‐based management is a leading nonpesticidal strategy among integrated pest management options. Improving the potency of pheromone products by adding synergists would be a practical way to popularize pheromone‐based management as well as to reduce pesticide use.RESULTSUsing reverse chemical ecology, synergists for Grapholita molesta sex pheromone were screened. Combined molecular docking and in vitro binding assay led to the determination of four potentially active odorants showing high affinity to G. molesta pheromone binding protein 2 (GmolPBP2). Thereafter, the high affinity between Codlemone and GmolPBP2 was further verified by exploration of GmolPBP2–Codlemone interactions. As the only sex pheromone synergist validated by both laboratory behavioral tests and field trapping, Codlemone was used to optimize commercial sex attractants currently used in G. molesta control. The recommended formulation [(Z)‐8‐dodecenyl acetate:(E)‐8‐dodecenyl acetate:Codlemone = 95:4:10] was found to trap about five to six times more G. molesta adults than the commercial sex attractant [(Z)‐8‐dodecenyl acetate:(E)‐8‐dodecenyl acetate: (Z)‐8‐dodecenol = 95:4:1].CONCLUSIONCodlemone is an excellent pheromone synergist that can be potentially sensed by GmolPBP2, which can remarkably improve the potency of G. molesta sex attractants. It is believed that the introduction of reverse chemical ecology would increase the chance of discovering pheromone synergists, promoting the development of more efficacious pheromone products that can be used in controlling G. molesta and beyond. © 2021 Society of Chemical Industry.