The invention provides 1,2,5-oxadiazole-2 oxide analogue with a structure shown as general formula I, and a preparation method and an application thereof. The 1,2,5-oxadiazole-2 oxide analogue has the activity for resisting schistosome thioredoxin glutathione reductase, kills schistosome by blocking a normal redox equilibrium physiological metabolism process of schistosome cells, can be used as a drug lead for development of drugs for treating schistosomiasis, and provides novel means for preventing and treating schistosomiasis. The general formula I is shown in the description.