The 55-year-old singer said on Monday's episode of Andy Cohen Live that it's "heartbreaking" to see Pitt face "unfounded" child abuse allegations amid his split from Jolie.
"It breaks my heart that anyone would take something as personal as your marriage, your relationship and your rights to your children and do it as purposefully as I see it being done, because there's a way to be," Etheridge said.
"I've gone through family courts. I've been twice around this block, and I know it really well, and I know when there's some forethought to just how mean and just how you're going to put disinformation out there first," she added.
Jolie and Pitt called it quits in September after two years of marriage and more than a decade together. Sources claimed the actress filed for divorce after Pitt was abusive toward their children, and the FBI later confirmed it was evaluating an alleged incident.
"Nobody does that. You don't do that," Etheridge said of the allegations. "Completely unfounded. It's really heartbreaking to see that. I really hope he reaches back out because there are a lot of us who haven't seen him in ten years."
"We lost a friend," she added. "I was around when Angelina was not doing nice things with Billy Bob [Thornton] to Laura Dern. I went through that on a personal level ... It's crazy [how Angelina is during a breakup]."
Etheridge had revealed in March that she once counted Pitt as "such a good friend" that she considered him as a sperm donor, but rejected him because he wanted kids of his own. Pitt and Jolie share six children and reached a temporary custody agreement last week.