The Belgian winger was fouled on numerous occasions as the Blues ran out 2-0 winners against Wigan at the DW Stadium.
Reflecting on the high number of incidents, Di Matteo has warned the youngster that he may face similar treatment from other teams.
"He was certainly targeted, but I don't think there was any malicious intent by the Wigan players," Di Matteo told a press conference.
"It's just difficult to mark players like that."
Hazard joined Chelsea from French side Lille for £32m earlier this summer.