Both teams are currently in the bottom four with only three points separating them. Scunthorpe are two points ahead of Plymouth, who are only one point clear of Rye House and Redcar, the two teams below them in the table.
Plymouth team manager Lee Trigger said: “We did not want to be in this situation because we had hopes of getting into the play-offs again this season.
“But now we face our old rivals Scunthorpe with memories of meetings against them a few years ago when we were both in what was then the Conference League.
“We will be looking for a win against them on Saturday to avoid finishing the season on a losing note – and I certainly don’t want us to finish bottom of the table.”