Herein, we reported a general, convenient, and efficient synthesis of 3,5-disubstituted-1,2,4-oxadiazoles via cyclodehydration of O-acylamidoximes in the superbase system MOH/DMSO (M = Li, Na, K). Excellent isolated yields (up to 98%) were attained within short reaction times (10-20 min). In addition, mild reaction conditions and a simple work-up procedure allow the synthesis of a wide range of heat-labile 1,2,4-oxadiazole-containing substances.