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The application of some reported inhibitors against the chitinolytic enzyme OfChtI was limited due to their unsatisfactory insecticidal activities. Hence, we first performed a synergetic design strategy combining the π-stacking effect with aqueous solubility to find novel rhodanine analogues with inhibitory activities against OfChtI. Novel rhodanine compounds IAa–fand IBa–fhave weak aqueous solubility, but they (IAd: Ki= 4.0 μM; IBd: Ki= 2.2 μM) showed better inhibitory activities against OfChtI and comparable insecticidal efficiency toward Ostrinia furnacaliscompared to the high aqueous solubility compounds IIAa–fand IIBa–f(IIAd: Ki= 21.6 μM; IIBd: Ki= 14.3 μM) without a large conjugate plane. Further optimized compounds IIIAa–jwith a conjugate plane as well as a higher aqueous solubility exhibited similar good inhibitory activities against OfChtI (IIIAe: Ki= 2.4 μM) and better insecticidal potency (IIIAe: mortality rate of 63.33%) compared to compounds IAa–fand IBa–f, respectively. Molecular docking studies indicated that the conjugate planarity with the π-stacking effect for rhodanine analogues is responsible for their enzyme inhibitory activity against OfChtI. This study provides a new strategy for designing insect chitinolytic enzyme inhibitors as insect growth regulators for pest control.