City will book their place in the knockout phase with victory over Gladbach, having won the reverse fixture in mid-September.
City, second in Group C behind leaders Barcelona, will book their place in the knockout phase with victory over Gladbach, having won the reverse fixture 4-0 when Sergio Aguero scored a hat-trick in mid-September.
The 28-year-old striker revels in clashes against German clubs.
He also scored on his last visit to Borussia Park in September 2015, converting a 90th-minute penalty to earn City a 2-1 win, and netted a hat-trick in a 3-2 victory at home to Bayern Munich in November 2014.
This is the first time Guardiola has returned to Germany for a competitive game since he quit Bayern Munich in May after winning seven titles in three seasons.
Guardiola's City are third in the Premier League table and fresh from Saturday's 2-1 win at Crystal Palace.
Yaya Toure marked his shock return after three months on the sidelines with both goals but is not eligible for Europe.
Guardiola rested Ilkay Gundogan against Palace and only used David Silva off the bench, a hint that both may feature at Borussia Park.
This is a case of win or bust for Gladbach's Champions League aspirations.
An unlikely victory would lift Gladbach level with City on seven points before Borussia's daunting final group match away to Barcelona on December 6.
Moenchengladbach will be confirmed in third place -- which means passage into the last 32 of the Europa League -- if they draw and Celtic lose at home to Barcelona, also on Wednesday night.
But Gladbach are not in good form. Their 2-1 defeat at home to Cologne on Saturday left them 13th in Germany's top flight after just one win in their past six home games.
But Andre Schubert's side led Barcelona at Borussia Park until two second-half goals dug the Group C leaders out of trouble for a 2-1 win in September and Gladbach need another brave performance at home.
US international Fabian Johnson has urged his Moenchengladbach team-mates to forget recent results.
"We need to try and clear our heads and look forward in a positive frame of mind," said Johnson. "After all, it?s not as if we've played badly in every game recently.
"We need to try to take the positives into the game against Manchester City.
"It's a different competition and everyone is looking forward to facing another top team with great players in the Champions League."
It will be interesting to see whether Guardiola recalls midfielders Gundogan and Leroy Sane, former Borussia Dortmund and Schalke 04 stars, who both know Borussia Park well.