The invention discloses a preparation method of a tetrahydroglyoxaline inhibitor applicable to a 
drilling fluid. The preparation method comprises the following steps of a, adding 150mL of substance A,150mL of substance B and 26.8g of substance C in a 
beaker; b, using 8 to 12mL of water for dissolving 7.6g of substance D, and dropwise adding 1 to 2 drops of 
sodium hydroxide solution; c, using thesodium 
hydroxide solution for adjusting a pH value of a reaction mixture to 8, filtering for removing separated white 
solid, distilling off the substance A, the substance B and water, and obtaining apale yellow 
viscous liquid; d, using 
chloroform for extracting to obtain a product 1; e, adding 13.6g of product 1 and 7.4g of substance E in to a three-necked flask, and obtaining an orange-yellow viscous transparent liquid; f, using 
ethyl acetate as an eluent, and obtaining a product 2; g, adding 60mL of substance B and 5.8g of substance F into the three-necked flask, and obtaining a pale yellowviscous liquid; h, extracting with 
acetone, removing a 
solvent, using 
benzene for recrystallizing, and obtaining a white product. The 
polyamide inhibitor prepared by adopting the method has the characteristics of high 
temperature resistance, remarkable 
inhibitory effect, less influence on rheological property, and the like, and is applicable to various water-based 
drilling fluid systems.