Giardino was born in Bologna, where he graduated in electrical engineering in 1969. At the age of 30, he decided to leave his job and devote himself to comics. Two years later his first short story, "Pax Romana", was published in La Città Futura, a weekly magazine published by the Italian Communist Youth Federation and edited by Luigi Bernardi.
In 1982 Giardino created a new character: Max Fridman, an ex-secret agent involved in the political struggle in 1930s Europe. His first adventure, Hungarian Rhapsody was serialized in the first four issues of magazine Orient Express, bringing Giardino in the limelight of the international comic scene. Max Fridman adventures have been published in 18 countries. Some of the prizes the series won include Lucca Festival's Yellow Kid (de) and Brussels' St. Michel.
Starting in 1984, Giardino produced a number of short stories for the Italian magazine Comic Art, where he introduced Little Ego, a young and sexy girl inspired by Winsor McCay's Little Nemo who stars in one-page dreamy erotic stories.
In 1991 Giardino created a new character, Jonas Fink for the Il Grifo magazine. Jonas is a young Jew in 1950's Prague whose father is arrested by the communist police. He and his mother have to cope with the discrimination and oppression of the Stalinist regime. The book, collected as A Jew in Communist Prague, won the Angoulème Alfred prize for best foreign work in 1995 as well as a Harvey Award at San Diego in 1999.
Giardino detailed art style recalls the French ligne claire, while his writing owes to hard boiled and spy story authors like Dashiell Hammett and John le Carré.