Abstract: As invasive species,Spartina alterniflora, affect adversely the coastal tidal ecosystem in China. Selecting effective herbicides is a low-cost control method. In this study, two herbicides, glyphosate and glufosinate, were selected according to previous studies. Pot experiment and field experiment were conducted to study the effects of dose and compound combination of herbicides on Spartina alterniflora. The biosafety of benthic organisms of Mactra veneriformis and Cyclina sinensis, was evaluated by culture experiment. Results showed that the effect of glufosinate was better than that of glyphosate. The optimal dosage was 150% recommended by the manufacturer. However, the mortality of cordgrass using single chemical was only about 20%. Combination of herbicides significantly increased the mortality and reduced the biomass of cordgrass. The optimal dosage for the combination of glyphosate and glufosinate was 9 450 mL/hm² and 13 500 mL/hm², respectively. As result, the mortality of compound herbicides treatments reached 90%. The biosafety evaluation test showed that no mortality of herbicides occurred to the native benthos though it enriched slightly in benthic organisms. The chemical control of Spartina alterniflora and biosafety evaluation in coastal wetlands in this study can provide reference for future control of cordgrass.