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The D.338 was a development of the D.333 with retractable undercarriage. First flown in 1936 it had a slightly increased wingspan, and the fuselage was lengthened by 3.18 m (10 ft 5¼ in). For short routes, the aircraft could carry 22 passengers, aircraft used in the Far East were fitted with 12 luxury seats, including six that could be converted into sleeping berths.

The D.338 had a reputation for reliability and was used during World War II in the French overseas possessions. Nine aircraft that survived the war were operated on the Paris-Nice service for several months.

The Argentine Air Force operated two Dewoitine 338s after World War II: F-AQBT Ville de Chartres was given the military registration T 170 and F-AQBR Ville de Pau became T 171. Both planes flew until the late 1940s.