The eldest of six children, Juan Luis Galiardo Comes was born in San Roque, Cádiz, but spent most of his childhood and youth in Badajoz, where his father had moved following working opportunities. After finishing his secondary education in Seville, Galiardo studied Agricultural Engineering at the University of Madrid. He abandoned his studies in 1961, to enroll the following year at Spain's National Film School (EOC) where he trained as an actor. He began his career working in the theater under the direction of José Luis Alonso de Santos in the theater María Guerrero. With some fellow actors he founded the T.E.I. (Independent Experimental Theatre), directed by Miguel Narros.

Galiardo made his film debut in the leading role in Julio Diamante's film El arte de vivir (The Art of Living) (1965). In the next sixteen years he appeared in more than fifty motion pictures, becoming one of the most popular romantic lead actors of Spanish films thanks in great part to his matinee idol good looks. Among his film of this period are notable his performances in Carlos Saura's Stress es tres, tres (Stress is three, three) (1968), Vicente Aranda's Clara es el precio (Clara is the Price) (1974), and two films by Jaime Camino: Mañana será otro dia (Tomorrow is another day) (1966) and La campanada (Pealing of the Bells) (1980).

In 1979, Galiardo went to Mexico where he lived for five years, appearing in secondary roles in Mexican films as well as in popular television dramas. In 1982 he received the Heraldo award as best actor

With his work in television in Turno de oficio (1986- 1987), Galiardo began to break away from his previous image of leading-man, accepting more dramatic roles and showing a wider range in this, the third phase of his career. He co-starred in some big projects both in film and television as in La Regenta, a production for TVE directed by Fernando Mendez-Leite. Among his most notable films are: Soldadito español (1988); Guarapo (1989), Don Juan, mi querido fantasma (1989); Madregilda (1993), Familia (1996) directed by Fernando León de Aranoa Pajarico (1997) a film directed by Carlos Saura; Adiós con el corazón (1999), a film directed by José Luis García Sánchez for which Galiardo won the Goya Award as best actor in 2000; Lázaro de Tormes (2000); El caballero Don Quijote (2001) and Miguel y william (2007). His roles in this two last films allowed him to be the only actor to play both Miguel de Cervantes and his most famous creation Don Quijote de la Mancha.

In 2007 he played Fidel Castro in I Love Miami a parody of the famous dictator possible FLIGHT to Miami as just another rafter. The following year Galirado played an important role in the gay themed film Clandestinos, who raised some controversy mainly due to the promotional image of the film. His last film was La chispa de la vida (2010) under the direction of Alex de la Iglesia. He died, aged 72, in Madrid of lung cancer.