"There's going to be two principles at play here, and one is, I'll speak for myself, I'll speak for the 49ers, we will not tolerate domestic violence," Harbaugh said. "Second principle is we're firm believers in due process. And I ask for your understanding on those two principles."
Harbaugh would not say whether McDonald would be allowed to practice this week or play in this weekend's season opener at the Dallas Cowboys, although he did reiterate his stance on the charges.
"If someone physically abuses a woman and/or physically or mentally abuses or hurts a child, then there's no understanding," he said. "There's no tolerance for that."
McDonald was jailed on felony domestic violence charges and was in the custody of the Santa Clara Sheriff's Department before posting bail Sunday afternoon.
He wouldn't discuss what happened with television news reporters who approached him after he posted bail.
"I can't say too much, not right now, but the truth will come out," McDonald said Sunday. "Everybody knows the kind of person that I am. I'm a good-hearted person."
On Tuesday, Harbaugh said he would not want someone guilty of domestic violence on the team.
He was also asked about former 49ers safety Donte Whitner's comment from last season: "He said that we can do anything in the world and we can come and talk to him and he'll forgive us except put our hands on women. If you put your hand on a woman, then you're done in his book."
Harbaugh's response: "You don't need a source to know how I feel."
"I'm strongly opposed to domestic violence or violence to children," he said. "It will not be tolerated."
Asked whether he had a comment on the 49ers' league-leading 10 arrests since 2012, Harbaugh said: "We're going to do everything in our power to make sure there isn't a pattern forming."
McDonald's incident occurred less than three days after NFL commissioner Roger Goodell announced tougher penalties for players who are convicted of or reach a plea agreement after domestic violence. Under the league's newly implemented personal conduct policy, a first domestic violence offense will result in a six-game ban and a second in a lifetime ban from the NFL.