Interlayers play a vital role in achieving high efficiency and stability of organic solar cells (OSCs). Zinc oxide (ZnO) has been widely used as an electron transport layer (ETL) in inverted OSCs; however, its high structural defects and intrinsic photocatalytic nature toward nonfullerene acceptors limit its applications in OSCs. Herein, a low-cost, environmentally-friendly biomolecule, potassium aspartic acid (PAA), is introduced as the interlayer on top of the ZnO ETL. Through experimental results and theoretical calculations, we find PAA not only can tune energy alignments and passivate oxygen vacancy defects and zinc interstitial dangling bonds but also can promote the π–π stacking strength of the active layer, leading to enhanced charge collection and photovoltaic performance in both IT series (e.g., PM6:IT-4F) and Y series (e.g., PM6:BTP-4F-C5-16) OSCs. Moreover, benefiting from the reduced surface defects of ZnO, OSCs based upon the ZnO/PAA ETL exhibit superior stabilities under continuous operation as well as UV-light irradiation, leading to an improved T80 lifetime of around 4 times compared to OSCs fabricated without the PAA interlayer. This work provides a universal solution to fabricate efficient and stable inverted OSCs.