The 38-year-old made his announcement in a video posted to Instagram after concluding his P2 campaign in the IMSA SportsCar Championship with TDS Racing.
"Today I say goodbye to racing," said van der Garde, who took a P2 class win in the World Endurance Championship's Portimao round earlier this year for United Autosport.
"A little sad? Maybe, but proud and happy all the same. It has been quite a ride."
The Dutchman cited a desire to spend more time with his family and to focus on his work as an F1 pundit for Viaplay and other entrepreneurial interests.
After winning the world karting title in 2002, van der Garde claimed the Formula Renault 3.5 title in 2008 before embarking on four years in GP2.
He completed only a single season in F1, starting 19 grands prix for the tail-end Caterham outfit in 2013, but had a valid contract to race for Sauber in 2015 after spending a year as its reserve driver before the Swiss team engaged Marcus Ericsson and Felipe Nasr instead.
Van der Garde successfully took Sauber to court, but it marked the end of his single-seater career.
He subsequently won the European Le Mans Series title in 2016 for Jota Sport, and then forged a lengthy partnership with Racing Team Nederland's Frits van Eerd between 2018 and 2022, which peaked with van Eerd winning the WEC's P2 pro-am title in 2021.
The duo also finished second in P2 in the Daytona 24 Hours and Sebring 12 Hours last season.
Van der Garde brought the curtain down on his career by finishing second in class at Petit Le Mans in October.
Speaking to Autosport's sister title GP Racing earlier this year, van der Garde explained that 2015 had been "the most difficult time ever in my life" but stressed that "the whole situation makes you also stronger as a person".
"It was a bad time for me," he said. "I wanted to be one of the race drivers, and I had a signed contract and suddenly they put two other drivers in.
"It was very tough. But sometimes Formula 1 is unpredictable and it goes like it goes and you cannot handle like the way you wanted.
"At that time money was very much the problem for the team, they needed to have that money to survive.
"It was a pity because I think if I would have had that drive that year, I think I would have had a nice season, especially I might have taken some points.
"I never could show the world what my capability is, and be consistently into the points."
