The effects of pollutants on anaerobic fermentation of waste activated sludge (WAS) have been widely studied. Nevertheless, little attention was paid to how to mitigate the adverse effects of pollutants on anaerobic fermentation. In this work, representative pollutant carbamazepine (CBZ) was chosen to explore the potential effects of CBZ on WAS anaerobic fermentation. Experimental results showed that CBZ at environmental levels slightly promoted the production of short-chain fatty acids (SCFAs), which increased from 3858.2 to 4143.8 mg COD/L as the CBZ dose increased from 8 to 28 mg/kg VSS, but further increasing the CBZ dose to 88 mg/kg VSS decreased the production of SCFAs. Context of homologous group database revealed that the abundance of some functional traits changed, such as RNA processing and modification, energy production and conversion, and amino acid transport. This adverse effect was sustained because CBZ could not be degraded during anaerobic fermentation. Therefore, a regulation strategy was proposed, e.g., persulfate was used to attenuate the toxicity of CBZ to WAS anaerobic fermentation, and the results showed that the removal of CBZ reached 83.7% in the persulfate-treated reactor. Based on density functional theory and metabolic intermediates determination, hydroxylation and deamination reactions were the two main metabolic pathways for CBZ degradation.