Spurs moved for the winger on deadline day, agreeing a loan with a £75m option to buy next summer, after their attack had misfired badly in the opening two league games of the season.
Mudryk has not featured competitively since November 2024, when a positive test for the banned substance meldonium triggered a lengthy doping case that only concluded in July, when the FA and the World Anti-Doping Agency agreed to resolve the matter and clear him to play again immediately.
The 25-year-old has since returned to training and featured briefly for Chelsea during their pre-season tour of Australia and Asia, and was included in Tottenham's Premier League squad list this week.
De Zerbi confirmed on Friday that Mudryk is unlikely to be ready to start against Nottingham Forest but could feature from the bench.
"He needs time to be able to start," the head coach said. "To play one part of the game, he's ready right now to play 15-20 minutes."
De Zerbi worked with Mudryk previously at Shakhtar Donetsk, where he once tipped the winger to eventually win the Ballon d'Or — a prediction he was keen to put into context rather than repeat as pressure ahead of his Tottenham reintroduction.
"We spent a very particular season together at Shakhtar. When I spoke about the Ballon d'Or I was very clear, I was speaking about the potential of the player," De Zerbi said.
"The player can respect the prediction or not. He has had plenty of problems, most recently the ban. He has plenty of qualities though and he needs to feel this season in the right way, not too much pressure. It's the right time for him to show why Chelsea spent 100m on him. I think he's ready to play part of the game."
Mudryk joined Chelsea from Shakhtar for an initial £88.5m in January 2023 but struggled to justify that outlay before his ban brought his career to an abrupt halt, having made just 73 appearances in all competitions for the club, scoring 10 goals and adding nine assists.
The suspension had originally been set at four years, before the FA's agreement with WADA — reflecting subsequent changes to how meldonium concentrations are assessed — allowed him to resume his career more than two years early.