Perovskite solar cells (PSCs) have attracted extensive attention in photovoltaic applications owing to their superior efficiency, and the buried interface plays a significant role in determining the efficiency and stability of PSCs. Herein, a plant-derived small molecule, ergothioneine (ET), is adopted to heal the defective buried interface of CsPbIBr 2 -based PSC to improve power conversion efficiency (PCE). Because of the strong interaction between Lewis base groups (−C�O and − C�S) in ET and uncoordinated Pb 2+ in the perovskite film from the theoretical simulations and experimental results, the defect density of the CsPbIBr 2 perovskite film is significantly reduced, and therefore, the nonradiative recombination in the corresponding device is simultaneously suppressed. Consequently, the target device achieves a high PCE of 11.13% with an open-circuit voltage (V OC ) of 1.325 V for hole-free, carbon-based CsPbIBr 2 PSCs and 14.56% with a V OC of 1.308 V for CsPbI 2 Br PSCs. Furthermore, because of the increased ion migration energy, the detrimental phase segregation in this mixed-halide perovskite is weakened, delivering excellent long-term stability for the unencapsulated device in ambient conditions over 70 days with a 96% retention rate of initial efficiency.