Guillén or Guillen is a Spanish or French surname. Notable people with the surname include:
- Alanis Guillen (born 1998), Brazilian actress.
- Ambrosio Guillen (1929–1953), United States Marine who was posthumously awarded the Medal of Honor
- Amparo Guillén (1953–2024), Ecuadorian actress
- Carlos Guillén, retired Venezuelan baseball player
- Charlie Guillen, American writer and filmmaker
- Fernando Guillén (disambiguation), multiple people
- Harvey Guillén (born 1990), actor
- Jorge Guillén, Spanish poet
- José Guillén (born 1976), Dominican baseball player
- Juan Manuel Guillén, El Salvadoran artist, digital producer for LCBO
- Laurice Guillén (born 1947), Filipina actress
- Montserrat Guillén (born 1964), Spanish statistician and economist
- Nancy Guillén (born 1976), retired Salvadoran hammer thrower
- Néstor Guillén Olmos (1890–1966), President of Bolivia for 27 days
- Nicolás Guillén, Afro-Cuban poet
- Ozzie Guillén (born 1964), Venezuelan baseball coach and former player
- Osiel Cárdenas Guillén (born 1967), Mexican drug lord
- Rafael Guillen ("Subcomandante Marcos"), spokesman for the Zapatista Army of National Liberation
- Ricardo Guillén (born 1967), Spanish basketball player
- Sammy Guillen (1924–2013), West Indian and New Zealand cricket player
- Tonatiuh Guillén López, Mexican academic and government official, Mexico's immigration chief since December 2018
- Vanessa Guillen, American soldier
- Walter Guillén Soto, Catholic bishop in Honduras
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