The versatile midfielder moved to Galatasaray from Borussia Dortmund in September but was unable to play for the Turkish champions, who failed to complete his registration before the Super Lig deadline.
The 27-year-old ended his brief, abortive stay in Turkey and returned to the Bundesliga with Stuttgart earlier this month but Low has said Grosskreutz's lack of football will make a call-up for the European Championship impossible.
He also criticised the player for his attitude during the ill-fated Galatasaray switch.
When asked if Grosskreutz could still earn a spot at Euro 2016, Low, speaking at a German Football League (DFL) event, said: "No. He hasn't played for a year and a half now.
"I was in Istanbul and talked with the Galatasaray coach, who told me that Kevin flew home nearly every weekend from Friday to Sunday. You don't do that when you are part of a team."
"I have limited comprehension over how he has handled his career."
Grosskreutz was part of Low's World Cup-winning squad in 2014 but failed to make an appearance at the finals in Brazil.