The invention discloses a method for preparing a cis-2,5-disubstituted 1,3,4-oxadiazepine compound under mild alkaline conditions. The method mainly comprises: adding a phenol derivative, imine, a 4[angstrom] molecular sieve and cesium carbonate to an organic solvent, heating to a temperature of 50-80 DEG C, carrying out a reaction, and carrying out post-treatment after completing the reaction toobtain the cis-2,5-disubstituted 1,3,4-oxadiazepine compound. According to the present invention, the preparation method has advantages of good product stereoselectivity, simple operation and easily-available raw materials, is insensitive to air and water, can avoid the use of toxic heavy metal catalysts, can be conveniently enlarged to the gram level, can further synthesize diversifiedly-substituted 1,3,4-oxadiazepine compounds with different substitution positions through the design, and further has characteristics of convenient operation and expanded applicability.