This study systematically investigated the electrooxidation of 17β-estradiol (E2) and inhibition of formation of fulvic acid (FA) aggregation in reactive electrochemical membrane (REM) made of Ti₄O₇. Our results indicate that aggregated FA in the membrane could retard the breakthrough rate of E2, while the interception for E2 was significantly alleviated for treated FA due to its structural change during REM electrooxidation. The electrooxidation removal efficiency of E2 during REM operation increased with the decrease of permeate flow rates due to the longer residence time within REM, and 95.90 ± 0.92% removal was reached at 20 mA cm⁻² with the permeate flow rate of 7.5 mL min⁻¹. FA inhibited the electrooxidation of E2 accompanied by the generation of specific intermediate products. Our results involving designed experiments and molecular simulation calculation indicated that direct electron transfer (DET) reaction induced polymer generation, and the generation of hydroxylation and ring-opening products was initiated by the reaction with hydroxyl radicals (^•OH). Permeate flux analysis and excitation-emission matrix characterization indicated that significant antifouling performance of REM was mainly attributed to the structural change of FA during REM treatment. These results revealed the potential roles of natural organic matter in Ti₄O₇ REM treatment of organic contaminants that greatly promoted the development of REM operation application.