Antidepressants accumulate in the aquatic environment due to human wastes. “Here, microbial fuel cell (MFC) technology is investigated as a candidate for elimination of antidepressants introduced into environment via human wastewaters.” Human urine containing selective serotonin reuptake inhibitors (paroxetine) and serotonin‐norepinephrine reuptake inhibitors (venlafaxine, O‐desmethylvenlafaxine (ODV)) are used as substrates in MFCs. Electricity production by the MFCs is monitored while simultaneous drug degradation is analyzed using liquid chromatography‐tandem mass spectrometry. When the human urine samples containing drugs (10 or 50 ng drug per mL) are treated in MFCs, electricity production decreases in response to increasing drug concentrations. Upon addition of drugs‐containing urine, chemical oxygen demand removal capacity of MFCs decreases from 54% to 37%. Mass spectrometry results show that drugs are degraded at a rate of 10 ng mL−1 per hour for paroxetine, 11 ng mL−1 per hour for venlafaxine, and 16 ng mL−1 per hour for ODV, i.e., 94% of paroxetine, 66% of venlafaxine, and 48% of ODV is cleared in 9 h of treatment. In conclusion, MFC exhibits great potential in elimination of paroxetine, venlafaxine, and ODV from wastewater. These results can help to develop sustainable strategies to combat antidepressant pollution.