Fan favourite Garde, who spent six years as a player with Lyon, replaced Claude Puel in the hotseat in 2011.
The 48-year-old struggled to compete with those vying for the Ligue 1 title due to a lack of spending power at the club over recent years, but still achieved success – guiding his side to Coupe de France and Trophee des champions titles in 2012.
However, the manager has revealed that he will not extend his contract with the Ligue 1 outfit and will depart in the coming weeks.
"Remi will end his contract, which anyway was expiring on June 3," president Jean-Michel Aulas told a news conference.
"I am leaving for personal and family reasons. I will not be the club's employee on July 1, but I will not go sit on another bench. What I need is a break," said Garde, who will have a say on who succeeds him.
French media outlet Canal+ report that Garde will take up another role at the club, though the rumours are yet to be confirmed.