Left-back Schmelzer and midfielder Gotze took part in training on Tuesday, having recovered from minor injuries that kept them out of the 2-1 Bundesliga defeat by Schalke 04 on Saturday.
"We assume they will both play, for Ilkay Guendogan I do not know yet," coach Jurgen Klopp told reporters on Tuesday.
Midfielder Gundogan was also sidelined against Schalke.
Dortmund are second in Group D with four points, two behind leaders Real and three ahead of Manchester City.
The Germans, who conceded a last-gasp equaliser in a 1-1 draw at City earlier this month, have already amassed as many points in two games as they did in the entire group stage last season.
"It will be a huge challenge for us," said a relaxed Klopp who joked with the translator and the reporters throughout his news conference.
Klopp said he was impressed by Real's 4-1 victory at group rivals Ajax on October 3.
"They had a highlight game in Amsterdam, they had everything," he explained. "Tactics, speed, pressing, high quality, top skills - I have seen them often but never as good as in that game.
"I think they are in good form, stronger than last year, we have to be extremely disciplined with the ball and we have to deal with some key players as well."
Klopp said Dortmund would counter Real's talent by rekindling the enthusiasm they showed against City.
He played down the absence of injured Real defender Marcelo, saying the depth of the Spanish team's squad would simply mean another world class player coming in.
"I do not know what my counterpart [Jose Mourinho] will do but I have the impression it is not a huge advantage for us," added Klopp.
