They remain unbeaten in the league while Saturday's opponents have seen their form nosedive since winning their first three Bundesliga games.
The international break was a mixed blessing for Bayern, with a number of players qualifying for the World Cup while also breaking personal records, although it also presented Guardiola with injury problems too.
Bastian Schweinsteiger collected his 100th international cap as Germany finished Group C unbeaten, while Franck Ribery and Arjen Robben were on target for France and the Netherlands respectively on Tuesday.
Mario Gotze, who scored for Germany against Sweden, could make his first start for the club since the 1-1 draw with Freiburg in August, although Xherdan Shaqiri faces six weeks on the sidelines after picking up a hamstring injury with Switzerland.
Toni Kroos believes team-mate Gotze is eager to show Bayern what they can expect from him after switching from Borussia Dortmund and hopes he can remain free of injury.
"After a long time he feels fit again," Kroos told the DFB website.
"For him the injury was difficult, just because he's at a new club where he wants to show, of course, where he wants to play. I'm happy for him and hope he stays fit now."
After being the early surprise package, Mainz failed to pick up a point in September with a draw against Hoffenheim last time out ending a five-game losing streak and putting them in 11th place.
While his side have gone five Bundesliga games without a win, Thomas Tuchel was just pleased to end the run of defeats.
"When you lose for so long, that hangs around in terms of points and self-confidence," Tuchel told the club's official website after the draw against Hoffenheim.
"It can take a while before things get back to normal. We've finally gotten that monkey off our backs."
Mainz's dip in form has, unsurprisingly, coincided with a dry spell in front of goal for leading goalscorer Nicolai Muller who has scored half of his side's league goals.
While Muller is joint top of the goalscoring charts in Germany, with six, he has scored just twice in Mainz's last five Bundesliga matches.
Tuchel is likely to need Muller to rediscover his scoring form if his side are to get anything against a Bayern team that have conceded just three league goals all season.
Mainz will be without Julian Koch (shoulder) for the clash, while defensive duo Niko Bungert (knee) and Bo Svensson (Achilles) are returning to fitness.