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The increasing use of herbicides in recent years for improved crop yields requires a risk assessment. To assess their impact on soil, the use of an indicator named the synthetic biological indicator (ISB%) is proposed, which includes a range of biotic and enzymatic parameters derived from previous experiments. Three sulfonylurea herbicides were evaluated, named chlorsulfuron, amidosulfuron, and tifensulfuron. The biotic and enzymatic parameters were monitored using different herbicide doses in field and laboratory experiments. Calculating this indicator for all experimental variants in the field and laboratory showed that the impact of the analyzed herbicides was insignificant, but there were statistically significant differences between the experimental conditions. The registration of an herbicide based on the legislation of different countries requires several toxicity tests of the active substance’s effects against soil microorganisms and some of the soil functions performed by microorganisms, parameters which are also included in the synthetic biological indicator (ISB). This indicator has the capacity to provide important information for sustainable soil management, including a minimum set of parameters, which can provide global information regarding the environment, showing changes in multiple areas of interest, including parameters that can be applied at minimal cost worldwide. In conclusion, we can say that the use of the indicator highlights all the changes caused by various soil chemical treatments because it follows the variation in a large number of parameters, unlike other indicators that follow only one, providing useful information for sustainable farming practices.