Mandzukic – who previously played in Serie A with Juventus – is a free agent after terminating his contract with Al-Duhail by mutual consent in July.
The Rossoneri are reportedly going to sign the Croatian striker on an 18-month deal, boosting their forward options as they look to maintain their push to win the league for the first time in a decade.
Pioli was not willing to discuss individual names at his pre-match news conference ahead of Monday's trip to Cagliari but did admit the club are ready to act if the right player becomes available.
"I don't want to and cannot comment on players that I don't have," he said. "I have a lot of confidence in the club and the management team. I leave that task to them.
"We know that if there is the possibility of strengthening the team, we will do it. We will be ready in January if there is the possibility of improving this group."
Milan have already made one signing in the mid-season transfer window, midfielder Soualiho Meite arriving on loan from Torino.
"Meite makes a department that already had good solidity even more competitive," Pioli said of the new recruit.
"I really liked the move. We have combined quality and quantity. I also liked how he spoke, saying he was ambitious. To join our group, you have to be like that."
Pioli admits it is a blow to be without the influential duo – they are also set to miss next Saturday's home fixture with Atalanta – but is confident he has the quality within his squad to cope with such situations during the course of the season.
"They are important absences, but this season is like that," the Milan boss said. "There are critical issues that can come at any moment, so we must always be prepared and attentive.
"The quality of the players that I will have available tomorrow will certainly make us have a good match.
"We are prepared, that's why I expect the players to always be ready. We can all be decisive and help the team."