The Belgium star limped off just before the hour in the midweek victory over Aston Villa with a muscular complaint.
A scan revealed the extent of the injury, with De Bruyne now set to miss key Premier League matches against Liverpool and Tottenham Hotspur next month as well as this weekend's FA Cup fourth-round tie at Cheltenham Town.
"The doctor said we'll review the scan today [Saturday AEDT] which we've done and it will be between four and six weeks out," Guardiola said.
"We have to move forward. I'm not saying anything nobody knows about how important it is, but unfortunately for him and all of us, he is out for an important part of the season.
"We have to find a solution as everyone is struggling and we have to adapt."
Meanwhile, Kyle Walker will also miss the Cup tie at fourth-tier Cheltenham after he too was forced off the field after suffering an injury against Villa.
But Guardiola was more upbeat about Walker's prospects, saying: "Kyle had a big impact kick in his hips, but it was just a kick. He's not available tomorrow but maybe for the next game."
Sergio Aguero has been ruled out of Sunday's (AEDT) match as well after the striker revealed on he had tested positive for COVID-19 during the week.
Guardiola added: "What we wish is for him [Aguero] to feel better. He felt uncomfortable for two or three days after his positive test, he felt quite tired and had symptoms. But he feels well and we want him to come back.
"For a long time we've missed our best striker. Like with Kevin we will have to manage until they come back."