Herein, we report the H2O2-mediated synthesis of 1,2,4-thiadiazole derivatives under metal-free conditions at room temperature with ethanol as the sole solvent. Various substrates could undergo the reaction smoothly, providing the expected yields of the desired products. Moreover, the target products were obtained by filtration or extraction instead of column chromatography, which requires a large amount of organic solution and silica gel during purification. The developed synthetic method can be potentially applied in the large-scale preparation of 1,2,4-thiadiazole derivatives as agrochemicals, pharmaceuticals, and functional materials.