Rookie cornerback Corey Ballentine (concussion) was also cleared.
Shepard has missed the past three games since suffering his second concussion in four weeks on Oct. 6 against the Minnesota Vikings. He will return after almost a month on the sideline.
The Giants (2-6) expected Shepard to be out a while after he reported symptoms the day after the loss to the Vikings. He has been practicing, mostly in a noncontact capacity, for most of the past three weeks. He was a full participant in practice this week.
Shepard's return gives the Giants and rookie quarterback Daniel Jones a full arsenal of weapons for the first time this year. Shepard, wide receiver Golden Tate, running back Saquon Barkley and tight end Evan Engram haven't been healthy and on the field together yet this season.
The Giants and doctors were cautious with Shepard. Before this season, he is believed to have suffered one concussion at Oklahoma and a pair in high school, per reports.
The symptoms from the second concussion this season dissipated quickly. That has provided Shepard some solace and, as a result, this isn't being viewed as a situation similar to that of Washington's Jordan Reed or even Indianapolis' Darius Leonard.
Reed's career is in jeopardy, and Leonard said he had symptoms that lingered for weeks.
Because of his concussion history, Shepard's absence covered multiple weeks, even if he wanted to return against the Arizona Cardinals two weeks ago.
"I'm not worried about it," Shepard told Newsday last week of the risks and long-term ramifications of concussions. "This is what I love to do and it's how I take care of my family. Yeah, I do have two kids and think about it from time to time, but I'll make that decision later on down the road."
Shepard was the Giants' leading receiver before the injury, with 25 catches for 267 yards and a touchdown.
The 26-year-old receiver signed a four-year, $41 million extension with the Giants this offseason.