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Wetlands and reservoirs are important water flow and storage regulators in a river basin; therefore, they can play a crucial role in mitigating flood and hydrological drought risks. Despite the advancement of river basin theory and modeling, our knowledge is still limited about the extent that these two regulators could have in performing such a role, especially under future climate extremes. To improve our understanding, we first developed a framework coupling wetlands and reservoir operations with a semi-spatially explicit hydrological model and then applied it in a case study involving a large river basin in Northeast China. The projection of future floods and hydrological droughts was performed using this framework during different periods (near-future: 2026–2050, mid-century: 2051–2075, and end-century: 2076–2100) under five future climate change scenarios. We found that the risk of future floods and hydrological droughts can vary across different periods, in particular, will experience relatively large increases and slight decreases. This large river basin will experience longer duration, larger peak flows and volume, and enhanced flashiness flood events than the historical period. Simultaneously, the hydrological droughts will be much more frequent with longer duration and more serious deficit. Therefore, the risk of floods and droughts will overall increase further under future climate change even under the combined influence of reservoirs and wetlands. These findings highlight the hydrological regulation function of wetlands and reservoirs and attest that the combining of wetlands with reservoir operation cannot fully eliminate the increasing future flood and drought risks. To improve a river basin's resilience to the risks under future climate change, we argue that implementation of wetland restoration and development of accurate forecasting systems for effective reservoir operation are of great importance. Furthermore, this study demonstrated a wetland-reservoir integrated modeling and assessment framework that is conducive to risk assessment of floods and hydrological droughts, which can be used for other river basins in the world. [ABSTRACT FROM AUTHOR]