Rookie quarterback Daniel Jones was ruled out for Sunday's game, marking the second game in a row he has missed because of a sprained ankle.
If Jones returns in time to start the Giants' Week 17 home game against the Philadelphia Eagles, Sunday could mark Manning's final home game in a Giants uniform.
The 38-year-old Manning started last week for the first time since Week 2. Although he fell to 0-3 on the season as a starter, he nearly helped pull off an upset over the Philadelphia Eagles.
Manning completed 15 of his 30 attempts for 203 yards with two touchdowns and no interceptions in the 23-17 overtime loss.
Overall this season, Manning owns a completion percentage of 59.7 percent with 759 yards, four touchdowns and two interceptions. The switch from Manning to Jones didn't produce many wins, as Jones is just 2-8, but he has shown flashes of brilliance with 2,374 yards, 18 touchdowns and 11 interceptions through the air, as well as 241 rushing yards and two rushing scores.
It is clear that Jones is the Giants' quarterback of the future, and with Manning's contract set to expire at the end of the season, he will likely either retire or play elsewhere in 2020.
If Sunday does prove to be the final home start or final start overall of Manning's 16-year tenure with the Giants, he will leave the fans with plenty of memories.
Manning is a four-time Pro Bowler and two-time Super Bowl champion with 56,740 passing yards, 364 touchdowns and 241 interceptions to his credit. Those accolades may be enough to land him in the Pro Football Hall of Fame one day.
The veteran signal-caller's goal Sunday will be to help the Giants improve on their 2-11 record this season against a Dolphins team that hasn't been much better at 3-10.
Sunday may mark the Giants best chance to win a game for the remainder of the season, and scoring a victory at home would be a fitting way for Manning to potentially end his Giants tenure.