Santoni is the surname of:

• Dante Santoni (born 1960), member of the Pennsylvania House of Representatives
• Elisa Santoni (born 1987), Italian rhythmic gymnast
• Félix Santoni, Puerto Rican politician and senator (1917–1920)
• Félix A. Santoni (born 1955), retired Army Maj. General and Puerto Rican shadow representative to the U.S. House of Representatives, Aug. 15, 2017 – Jan. 6, 2018
• François Santoni, suspected of being one of the leaders of Armata Corsa, a defunct separatist terrorist organization in Corsica
• Joël Santoni (born 1943), French film director and screenwriter
• Michael Santoni, Jr. (born 1964), professional wrestler under the ring name Big Guido
• Nicola Santoni (born 1979), Italian former football goalkeeper
• Reni Santoni (born 1939), American film, television and voice actor