Dortmund head to the Bernabeu boasting a one-point lead over Madrid at the top of Group D after beating Jose Mourinho's men 2-1 in Germany a fortnight ago.
Another victory would leave Dortmund within touching distance of a place in the last 16, but Schmelzer is not expecting an easy time of it against a Madrid side who have won seven successive Champions League matches on home soil while scoring an average of almost four goals per game, and whose only defeat in their last 10 competitive fixtures came at the hands of Jurgen Klopp's side.
"The Real players were all really angry after losing at our place and they are going to try to run us down, but we will resist," said Schmelzer, who scored the second goal against Madrid and was also on target in last week's 4-1 cup win over Aalen.
Schmelzer's team-mate Mats Hummels is also up for the fight, adding: "They will want revenge, but challenges like this are really exciting. I have no idea what to expect there, but the atmosphere is meant to be unique."
Dortmund will make a late decision on captain Sebastian Kehl, who has been training with a protective mask after breaking his nose against Stuttgart at the weekend.
Leo Bittencourt and Sven Bender both missed the Stuttgart draw, but have travelled to Madrid and are in contention to play.
Since losing to Dortmund, Madrid have racked up three successive victories in league and cup, scoring 13 times and conceding just once.
Real are still without full-backs Marcelo and Fabio Coentrao due to injury, but teenage defender Raphael Varane will be in the starting line-up.
Sami Khedira is missing due to a thigh problem and a similar injury has kept striker Karim Benzema out of Real's 20-man squad.