The Bío Bío River is the second largest river in Chile considering both discharge and length. The Bío Bío River flows through the second most important economical centre in Chile and it has been recently classified as one of the world's largest river systems strongly affected by fragmentation and change in flow regime, mainly due to hydropower and irrigation. The cities of Hualqui, Chiguayante, Concepción, Hualpén, and San Pedro de la Paz are located along the last 25 km of its course, and are exposed to a high flood risk due to a combination of increasing rainfall storms and the dams operation located in the upper basin. This work assessed several structural and non-structural flood defence alternatives for the lower 25 km of the river. A one-dimensional (1D) hydraulic model was used under different discharge scenarios. The results showed that storage areas and diversion canals located along the lower part of the Bío Bío River did not prove to be a suitable solution. Nevertheless, it was found that the most effective alternative implies a reservoir operation focused on storing the extra water produced by the incoming flood. Conclusions support the materialization of reservoir emergency operation protocols, as indicated in the Reglamento de Ley N°20.304, approved by Decreto de Ley 138, Chile.