Electro-Fenton (e-Fenton) reactions boosted using microbial fuel cells (MFCs) can degrade contaminants with high efficiency, the treatment is generally performed in the aqueous phase and the sludge pollution is ignored in such MFCs. In this study, a sediment MFC e-Fenton (SMFC-e-Fenton) system was proposed for the degradation of nonsteroidal anti-inflammatory drugs (NSAIDs) in both aqueous and solid phases. A Fe@Mn-codoped biochar gas diffusion cathode was fabricated to produce hydroxyl radicals without any additional power input. The studied NSAIDs of ibuprofen (IBU), naproxen (NPX), and diclofenac (DCF) exhibited total degradation efficiencies (including aqueous and sludge phase) of 99.1%, 98.5%, and 80.6%, respectively, in the SMFC-e-Fenton system. Compared with sludge anaerobic digestion, the residual amounts of IBU, NPX, and DCF reduced from 10.2%, 24.6%, and 32.2% to 2.7%, 4.4%, and 8.5%, respectively, in the sludge phase. Moreover, the electricity generation and sludge reduction improved owing to the e-Fenton process. Using the SMFC-e-Fenton system, the effects of NSAIDs were reduced and the richness and diversity of the microbial community are maintained, improving the overall system performance. These results demonstrate that the SMFC-e-Fenton method is a highefficiency, economic and environmental friendly technology for simultaneously treating NSAIDs in the aqueous and sludge phases.