To improve the biochemistry of wastewater and reduce organic sulfide and COD in garlic wastewater, the relationship between the interaction of coagulation environmental factors was clarified. Taking the high-concentration garlic wastewater as the object, the response surface method was used to analyze the effect of pollutant removal in garlic wastewater under the interaction of three environmental factors, namely, PAC dosage, pH and stirring speed. In the interaction, PAC dosage and pH > PAC dosage and stirring speed > stirring speed and pH, and PAC dosage had the most significant effect on the removal effect of organic sulfur and COD in the wastewater. Under the optimal coagulation conditions of PAC dosage of 1.54 g/L, pH value of 8.93, and stirring speed of 128.97 r/min, the actual removal rates of organic sulfur and COD were 96.21% and 22.89%, respectively, and the difference between the model predicted values and the measured values was less than 1%. The coagulation pretreatment can effectively remove organic sulfide and COD from the high-concentration garlic wastewater, and the BOD/COD increased from 0.34 to 0.44, which is conducive to the further degradation of organic matter in the biochemical section.