Their most recent home outing ended with an embarrassing 5-0 loss against rivals Liverpool.
United boss Ole Gunnar Solskjaer was reportedly given three matches to save his job after that defeat. The first saw his side win 3-0 at Tottenham Hotspur, with the second ending 2-2 away to Atalanta in the Champions League.
Solskjaer's men enter Saturday's clash in fifth place, three points behind fourth-placed West Ham United, whose goal difference is superior by five.
The Citizens are third in the table on 20 points, five behind leaders Chelsea.
Red Devils defender Raphael Varane will be out for around a month after sustaining a hamstring injury against Atalanta.
Fellow centre-back Victor Lindelof missed the game with a knock, but Solskjaer is hopeful that the Swedish international will be available.
Paul Pogba will serve the second of his three-match ban following his red card against Liverpool.
Guardiola will wait until his squad's training session on Friday before finalising his selection.
Kyle Walker was substituted against Brugge with a foot injury and will be assessed, with it still unclear whether he will be available.
Manchester United: De Gea; Lindelof, Bailly, Maguire; Wan-Bissaka, Fernandes, McTominay, Fred, Shaw; Ronaldo, Cavani.
Manchester City: Ederson; Walker, Dias, Stones, Cancelo; Silva, Rodri, De Bruyne; Jesus, Foden, Grealish.
Ones to watch
Cristiano Ronaldo was heavily linked with City in the summer before returning to Old Trafford and is United's one to watch on Saturday.
The Portuguese superstar enters the derby in fine form, scoring and assisting in the win at Spurs and netting a brace in the draw at Atalanta, including a last-minute equaliser.
He has faced the Citizens 14 times in his career and won nine of them, scoring five goals in the process.
However, he has only won four of his 16 games against a Guardiola side, with four draws and eight defeats while scoring seven.
City fan Phil Foden is their player to watch on Saturday.
The versatile youngster has five goals in all competition this season while also providing four assists.
He has mainly been operating as a false nine this campaign and will hope to help his side make the short journey home with all three points.
However, City are without a league win in this fixture in the last four meetings – with the Red Devils winning three of those.
Most recent meeting:
How to watch
The match starts at 12:30 GMT on Saturday 6 November 2021 and is available to watch on Sky Sports Main Event and Sky Sports Premier League.
What the managers have said
"It's a special one of course," Solskjaer said.
"The last time we had a Manchester derby with fans in the stadium, the atmosphere was electric.
"I think everyone will still remember that one, probably more so than any dark moments we’ve had. When Scott [McTominay] scored that goal in added time, it was a special moment.
"We know it’s a one-off game, it’s one of those you have to start on the front foot, start ready, because a lot of it depends who gets on the front foot.”
He continued: "I've got a great respect and admiration for Pep [Guardiola] and what he's done.
"We've had a few good results, tight games, we need another performance like this. Sometimes you need luck, we know this is a game where we'll have to work hard but we have to believe.
"We're at home, we've had a few good results, we need to work hard and we have to earn it. We have to go into this game believing we can do good things. It’s a local derby and everyone knows what’s at stake.”
On recent games against the Red Devils: “Congratulations to United for winning the duels against us,” Guardiola said.
“What they do is quite similar week by week. Incredible physicality, lots of talent and people up front who can win the game themselves.
“They have good runners in the channels and in behind, especially Fernandes who is good with the ball.
“We did good games against them, maybe not always a good result, except one game last season which was a little bit boring.
“They played five at the back and we were not in a good moment.
“In general we played good games. We were ourselves when we played them.
“Sometimes you win, sometimes you lose. United for the last century have been a good team.
“We are going to prepare well this afternoon and tomorrow morning.”
On Cristiano Ronaldo: “Normally I don’t talk about the players for other clubs. I am pretty sure he is happy to be at United and they are happy to have him.”
Guardiola was also asked about City's start to the season.
He said: “In 10 games we had two not good results against Southampton and Palace at home the rest we played well.
“The first one against Spurs we had eight or nine players of the first team missing.
“In general it was good. Always, even if you are winning many games in a row, you can improve.
“We will try to continue in this way.”