Indole and pyridine, which are highly produced refractory compounds in the industrial wastewater, exhibit poor degradation capabilities in natural environments. In this study, we developed an anaerobic digestion system coupled with weak electric mediation (ED), and investigated the promoting effect of weak electricity on indole and pyridine biodegradation. The degradation characteristics were systematically explored, and the results showed that the degradation rate and mineralization of indole and pyridine were significantly enhanced, the production of CH4 was increased 1.4-fold, and the optimal voltages were 1.0 V and 0.8 V in the ED, respectively. Moreover, simultaneous removal of carbon and nitrogen was achieved. Gas chromatography–mass spectrometry analysis verified the transformation products, and possible pathways were proposed. Several byproducts of indole and pyridine were identified, with oxindole and glutaric dialdehyde being the main metabolites, respectively. Additionally, density functional theory (DFT) analysis was performed to investigated the radical indices and stabilities of the molecules to further confirm the degradation pathway. Microbial structure analysis demonstrated that the electrically mediated enhanced metabolism and activity of functional microbes, led to the promotion of indole and pyridine mineralization. Moreover, such species as degrading bacteria (Alicycliphilus, Shinella) and electroactive bacteria (Achromobacter), anaerobic ammonia-oxidizing bacteria (SM1A02), and denitrifying bacteria (Thiobacillus) coexisted. This study demonstrates that weak electric mediation is a promising methodology for enhancing the removal of indole and pyridine from wastewater under anaerobic conditions.