Controlled synthesis of highly efficient, stable, and cost-effective oxygen reaction electrocatalysts with atomically-dispersed Me-Nx -C active sites through an effective strategy is highly desired for high-performance energy devices. Herein, based on regenerated silk fibroin dissolved in ferric chloride and zinc chloride aqueous solution, 2D porous carbon nanosheets with atomically-dispersed Fe-Nx -C active sites and very large specific surface area (≈2105 m2 g-1 ) are prepared through a simple thermal treatment process. Owing to the 2D porous structure with large surface area and atomic dispersion of Fe-Nx -C active sites, the as-prepared silk-derived carbon nanosheets show superior electrochemical activity toward the oxygen reduction reaction with a half-wave potential (E1/2 ) of 0.853 V, remarkable stability with only 11 mV loss in E1/2 after 30 000 cycles, as well as good catalytic activity toward the oxygen evolution reaction. This work provides a practical and effective approach for the synthesis of high-performance oxygen reaction catalysts towards advanced energy materials.