Kouzmanoff suffered a lower back strain during infield drills before an 8-0 loss to the New York Yankees at Yankee Stadium on June 17. He has missed the last five games.
Kouzmanoff will hit in his customary five-hole against the Twins.
"It feels good to just get back in the lineup and help the team win," Kouzmanoff said. "Nobody likes to sit the bench, not play and feel like you're not contributing. It feels good to get back in there."
Kouzmanoff is hitting .263 with 10 home runs and 33 RBIs on the season.
Giles is returning from a right hamstring injury he aggravated while trying to beat out a double-play ball in the sixth inning of Friday's win over the Detroit Tigers.
"Brian had a couple days over the weekend and his hamstring feels better," said Padres manager Bud Black.
Giles almost pinch-hit in Sunday's contest with the Tigers but, due to a pitching change, Giles was replaced with Tony Clark. Following that game, Tuesday was marked as the day for his return as well. Giles was slated to hit third.
On the season, Giles is hitting .297 with five home runs and 27 RBIs.
Ronald P. Clark is an associate reporter for MLB.com. This story was not subject to the approval of Major League Baseball or its clubs.