The 27-year-old has won eight stages in the past two years on the Tour and twice worn the yellow jersey but has been left out by Gian-Alpecint, who feel he is not yet fit enough to compete in the event.
"Of course I am disappointed about not participating in the Tour de France this year," said Kittel. "But I will have to look ahead and focus on new goals."
After racing at the Tour Down Under in Australia at the start of the season, Kittel went down with a virus in February that saw him miss two months.
He returned to action at the Tour de Yorkshire in May but abandoned less than 100km into the first stage. His best result this season remains a sixth-place finish at the Tour of Cologne on June 14.
"Good progress has been made in this process, however the team decided that Kittel's basic fitness is still not sufficient to compete in the Tour de France," the team said in a press release.
"An alternative racing program will be determined by the performance team and Kittel himself and new goals will be set for the autumn to structurally work towards them."
The Giant line-up will be led by John Degenkolb, who won this year's Milan-San Remo and Paris-Roubaix one day classics.
Kittel's absence also means the team could ride in support of Warren Barguil, who will be targeting a stage win in the mountains.
The 23-year-old Barguil, making his Tour de France debut, finished eighth overall in last year's Vuelta a Espana.
The Tour de France begins in the Dutch city of Utrecht on July 4 and finishes in Paris on July 26.
Giant-Apecin for the Tour de France:
Warren Barguil (FRA), Roy Curvers (NED), John Degenkolb (GER), Tom Dumoulin (NED), Simon Geschke (GER), Koen de Kort (NED), Georg Preidler (AUT), Ramon Sinkeldam (NED), Albert Timmer (NED)