City will make the short journey to OldTrafford on Sunday to face their arch-rivals, who are now one place behind and eight points behind them in the league.
But Guardiola who won the Champions League twice with Barceloan (2009 and 2011) admitted that City's impressive run in this season's competition is not a guarantee they will win it.
Kyle Walker, Vincent Kompany, Nicolas Otamendi, Fabian Delph, De Bruyne, Silva and Raheem Sterling did not play a single minute against Shakhtar, while Fernandinho only played 10 minutes on Sunday and Sane did not play against Southampton a week ago.
"I would think that Mourinho will play a more cautious game".
Midfielder De Bruyne said: "A derby is always special".
"Teams come to the Etihad now and defend so deep to try to frustrate, but I wish them all the best and hope they can win a lot of trophies at the end of the season".
Pep Guardiola's City are eight points clear at the top of the Premier League after a top-flight record of 13 successive wins in a season, with second-place United aiming to close the gap at Old Trafford.
Though City are assured of top spot, the game is a pivotal one for their hosts, with Shakhtar needing a point to secure progression at the expense of Napoli, who face pointless Feyenoord in their final group game.
Gale feels City pose too strong a threat for United to press and claims Guardiola's men could "pierce them apart".
He said: "Maybe (it is) good for me to get a little bit of rest and prepare myself for Sunday".
"They are doing great and have a great team".
The incident came after Raheem Sterling's late victor sent the Etihad into pandemonium, setting them up for a record-equalling 13th consecutive Premier League victory against West Ham on Sunday.
The Hammers are still awaiting their first win under new manager David Moyes.