The Madre de Dios River (Spanish pronunciation: [ˈmaðɾe ðe ðjos]) is a river shared by Bolivia and Peru which is homonymous to the Peruvian region it runs through.

The Madre de Dios is an important waterway for the department of Madre de Dios, particularly Puerto Maldonado, the largest town in the area, and the capital of the department.

Mango farming and gold mining are among the many industries on its banks.

Other important industries the Madre de Dios provides are selective logging and farming, both of which are serious environmental problems.

The river's main tributaries include on the right: Chivile, Azul, Blanco, Inambari, Tambopata and Colorado rivers and from the left: Los Amigos, Manu, and Las Piedras.