Abstract: To discovery novel acaricides based on natural products, twenty-six piperine derivatives containing 1,3,4-oxadiazoles ( 8a - 8z ) were designed and synthesized using piperine as a lead compound. Their structures were well characterized by ¹H NMR (¹³C NMR), IR and HRMS. The steric configuration of compound 8g was confirmed by single crystal X-ray diffraction analysis. Their acaricidal activities were tested against female adults of Tetranychus cinnabarinus Boisduval by slide-dipping method. Compounds 8m (LC₅₀: 0.41 mg/mL), 8r (LC₅₀: 0.36 mg/mL) and 8u (LC₅₀: 0.32 mg/mL) showed potent acaricidal activities which were 38.1, 43.4 and 48.9 folds of that of its precursor piperine (LC₅₀: 15.64 mg/mL). Moreover, compound 8u also showed good control effects on T. cinnabarinus in the greenhouse, and its control efficiency was 61.8% on the 5th day after treatment at 0.3 mg/mL. The SARs analysis showed that introduction of 1,3,4-oxadiazoles on the C2 position of piperine was beneficial to the acaricidal activity, and the acaricidal activity was also related with the substituents on the phenyl of 1,3,4-oxadiazoles.