The Frenchman was fourth in the general classification, 14 seconds behind the Spanish pink jersey Juan Pedro Lopez.
After his abandonment which occurred about an hour after the departure from Sanremo, the Auvergnat, pale-faced, took his place in the passenger seat of his DSM team's car.
RAI, the race broadcaster, explained his abandonment by stomach problems.
"After falling ill during yesterday's (Thursday) stage, the situation worsened overnight and despite all efforts, he is no longer in a position to continue the race," the DSM squad announced.
Bardet, 31, had made the Giro his first big goal of the season.
He had been present until this summer day, notably taking second place in the queen stage of the Blockhaus, last Sunday, in Abruzzo.
The rider from Brioude (Haute-Loire) then considered to be one of "the three best" of this Giro with the Ecuadorian Richard Carapaz and the Spaniard Mikel Landa.
The abandonment of Bardet is his second in twelve participations in the big tours.
His only retirement was due to a serious fall which had caused him a head injury in the Tour de France 2020.
Very consistent in his performance, he twice took a place on the Tour de France podium (2nd in 2016, 3rd in 2017) when he wore the colors of the team from his debut, the French formation AG2R La Mondiale. .
In the colors of the Dutch team DSM, which he joined at the start of 2021, he finished 7th in the Giro 2021 before winning a Vuelta stage.
This season, Bardet has multiplied training courses with a view to the Giro and won the Tour des Alpes in April.
DSM, which recently extended its two-year contract until the end of 2024, has not yet confirmed its presence in the next Tour de France, although its participation seems logical.
The 13th stage, which includes the ascent of a third category pass in the first part of the route, connects Sanremo to Cuneo (north-east) over 150 kilometers.
© 2022 AFP