Gholston, the team's first-round pick last year, didn't practice all week after tweaking his hamstring Monday in the Jets' first workouts following the bye-week break.
"He did not participate, so that's going to be very doubtful that he plays," coach Rex Ryan said.
Despite showing some improvement since his disappointing rookie season, Gholston is still looking for his first NFL sack. Gholston said he was feeling "a lot better" Friday, but the team was being cautious so it didn't turn into a more serious injury.
Smith hasn't played in the team's last three games after being injured at Miami on Oct 12. He was limited Friday, but listed as probable. If he plays, it'll be the first time quarterback Mark Sanchez has Smith, Jerricho Cotchery and David Clowney all healthy and available this season.
Sheppard has missed five of the last six games with his injury. Ryan said Sheppard won't start, but will play in a rotation with Dwight Lowery.
"Even though he's practiced fully, I don't think Lito's all the way back yet," Ryan said. "We'll evaluate to see how much he'll play. I think we'll start Dwight Lowery."