In the 1930s, Mathieu turned to furniture design, creating pieces for manufacturers such as La Maitrise and Atelier Matégot. He became famous for his use of modern materials such as metal, glass and plastic in his designs.
During the Second World War, Mathieu worked as a resistance fighter, hiding weapons and explosives in the furniture he made. After the war, he resumed his design career, creating furniture for major companies such as Air France and Compagnie des Wagons-Lits.
René Mathieu's creations have been exhibited in numerous museums and exhibitions, including the 1937 World's Fair in Paris. His work is considered an important example of mid-twentieth-century French design.