Dortmund had a rollercoaster first half to their campaign but earned their first away win in the Bundesliga this season - 3-1 at VfL Wolfsburg - in the last game before the break in December.
Victory over Leverkusen, in second place on 32 points, would see their gap cut to four points, with Dortmund currently in sixth on 25.
"For the table, it would be extremely important (to win the game) because we would close the gap," said Dortmund coach Nuri Sahin.
"We have so far delivered against top teams. We are playing at home and really want to win this game."
"The year starts with this game and it could be a good omen to get into a flow and pick up more points in the new year than we did in the first part of the season."
Dortmund, who face Bologna in the Champions League later in January, have not lost any of their last five matches against Leverkusen, including their rivals' unbeaten run to the Bundesliga title last year.
Sahin could be without Waldemar Anton, while suspended Pascal Gross and long-time injured Niklas Sule are out.
Their opponents are equally eager to hit the ground running this year with Leverkusen sports director Simon Rolfes, saying they were fighting for trophies in all their competitions.
Leverkusen won the domestic double without defeat last season and also reached the Europa League final.
"We want to win, also in Dortmund," said Rolfes, whose team is four points behind Bayern.
"We have the ambition and the will to win in Dortmund. It is this will that drives us."
"Realistically we have title chances in all competitions. To win titles you have to be there. We have the energy and will to give it all."
Bundesliga leaders Bayern have their own injury concerns ahead of Saturday's trip to Borussia Monchengladbach.
Keeper Manuel Neuer is racing to come back following a rib injury sustained in December, with second choice Daniel Peretz now ruled out after he needed medical treatment following a kidney injury suffered in training on Wednesday.
In-form Jamal Musiala missed Monday's friendly 6-0 win against RB Salzburg with an illness and it is still unclear if he can be ready to start on Saturday.
The Bavarians, in top spot on 36 points, have lost five of their last nine away games at Gladbach, more than against any other team in the same period.