Left-back Mendy missed most of last season with an anterior cruciate ligament rupture and is now out for up to three months after undergoing surgery on a fresh knee injury.
France head coach Didier Deschamps told the France international to take better care of his body last month and Guardiola agrees he must work to find a solution to his persistent fitness problems.
"I think he's a good professional. When he's there, on the pitch or in the locker room, he's doing what he has to do," said Guardiola.
"But we cannot deny that he had a big injury last season, he has another big injury right now and hopefully everyone can understand what you need to be.
"A strong guy is one who plays every three days. These kind of guys are never injured. That has to be his main target. After that we decide if he plays or not.
"Continuity is the target. He's young, incredible potential and it's a pity, an incredible guy.
"In two seasons it's a long time not playing for him."
Guardiola identified Fernandinho as one of his more robust players and, even though he conceded the Brazilian had his limitations, the former Barcelona coach reiterated he would not be dipping into the transfer market to buy further cover in the defensive midfield position.
"[Can Fernandinho play] every game? No way. He can play but we would kill him for the next season," added Guardiola. "He cannot play every three days, but we have alternatives.
"John [Stones], Danilo, [Fabian] Delph, [Oleksandr] Zinchenko, [Ilkay] Gundogan. We have a good squad and a few players can play in several different positions.
"We are not going into the transfer window. I am so delighted with the squad.
"I am sad when many players cannot play – imagine if I bring another one! It's better like this."