Nicks was held out of the Giants' first preseason game last weekend in Pittsburgh after missing a portion of training camp with a groin injury. He also is coming off an injury-plagued 2012 season, during which he attempted to play through foot and knee injuries.
Defensive end Justin Tuck will make his debut as well after missing last weekend's game because of tightness in his back.
Fellow defensive end Jason Pierre-Paul remains on the physically unable to perform list as he recovers from offseason back surgery. But coach Tom Coughlin is "encouraged" by what Pierre-Paul did Thursday, technically an off day for the team.
"If you saw him yesterday, he worked well yesterday," Coughlin said after practice Friday afternoon. "I think he's a little sore today, so they slowed him down again. But yesterday was an outstanding day. He ran well; he worked in the weight room."
The team remains hopeful Pierre-Paul will be ready to play by the team's regular-season opener Sept. 8 in Dallas.
Safety Antrel Rolle will not play against the Colts, either, as he recovers from a sprained ankle suffered earlier this week. Cornerback Terrell Thomas, working his way back from a third torn ACL, practiced Friday, but won't play until at least the team's third preseason game.
Cornerback Corey Webster, who missed the first two days of practice this week because of "soreness" from the Steelers game, returned to practice Wednesday, but then sat out again Friday.
"I think it's day to day," Coughlin said, adding that he hopes Webster can play Sunday.
Reserve tight end Larry Donnell suffered what looked to be a serious knee injury Friday. After making a nice catch down the field, Donnell landed awkwardly, stayed down and was quickly carted off.
Coughlin had no update on Donnell immediately after practice.
"He's gonna get all the tests," he said.
Rookie defensive end Damontre Moore, who made a big splash in the first preseason game, has not practiced this week because of a shoulder contusion. Wide receiver Jerrel Jernigan, running back Da'Rel Scott, offensive lineman Chris DeGeare and safety Cooper Taylor also did not practice Friday.
Coughlin said his first-teamers will play about 20 snaps Sunday, and the second-teamers about 25, before giving way to the rest of the roster.