Abstract: Natural products have the characteristics of novel structure, good activity, and low toxicity. The structural modification of natural products is an effective method to discover new green pesticides. In this research, 22 novel menthone oxime ester derivatives were designed and synthesized using the natural product menthone as the lead compound. The structures of the target compounds were confirmed by ¹H NMR, ¹³C NMR and HRMS. The biological activity results showed that the target compounds have certain antifungal activities against Valsa mali, Botrytis cinerea, Rhizoctonia solani and Fusarium oxysarum at 50 μg/mL. The structure-activity relationship showed that the Z-configuration of the compounds is more favorable for antifungal activities than the E-configuration. Especially, compounds B-2, B-6 and B-8 displayed good antifungal activities against V. mali with the EC₅₀ values of 4.92, 4.90 and 5.22 μg/mL, respectively, which were better than those of the lead compound menthone and the commercial fungicide trifloxystrobin ( 8.16 μg/mL).