The S.65 was a single-seat twin-engine floatplane of low-wing monoplane configuration with two floats.

Its tailplane was supported by two booms and the floats, which extended well toward the rear of the aircraft.

Its two 745-kilowatt (1,000-horsepower) Isotta Fraschini engines were mounted in tandem, each driving a two-bladed propeller, one in the nose in a tractor configuration and the other at the rear of the fuselage in a pusher configuration.

[1] The S.65 was excluded from the 1929 race due to mechanical problems, and Italy was instead represented in the race by one Macchi M.52R and two Macchi M.67 seaplanes.

[2] Tommaso Dal Molin of the Italian Schneider Trophy racing team was killed flying the S.65 during training at Lake Garda in northern Italy on January 18, 1930.