The pair both sat out Saturday’s draw against Hungary in Budapest with Gnabry resting a calf injury and Ruediger rested.
Ruediger, who transferred to Real Madrid from Chelsea earlier this month, is set to slot back in at centre-back with Bayern Munich winger Gnabry an option on the flanks in Moenchengladbach.
Germany have drawn 1-1 in all of their last four games against Hungary, England, Italy and the Netherlands dating back to March.
They are still chasing a first win in their Nations League group.
Flick admitted the squad is unhappy with recent results, but pointed out that he is bedding in new players with one eye on November’s World Cup in Qatar.
“In terms of our self-image, I don’t think the four draws are good – the players and I want to win,” Flick insisted in Monday’s press conference from Budapest.
“We want to decide games when it counts.
“We have six new players and are in the process of developing.
“Of course, there are setbacks, but then you do better next time.”
Germany started their Nations League campaign by drawing with the Italians in Bologna ten days ago.
The Germans sit third in Group A3, two points behind Italy who top the table.
Germany are near full-strength with only Dortmund playmaker Marco Reus out with a leg injury.