One segment of the interview, which took place on "The Rosie Show," had the two talk show hosts discussing their differing opinions of people with short stature. Basically, Handler loves them while O'Donnell is afraid of them.
"I'm a little ashamed about it [but] I have a mild fear or anxiety around little people," O'Donnell confessed before asking Handler point blank: "Would you ever do a little person?"
Handler's quick response: "No, that would be child abuse. I'd never do that."
"That's half my issue," O'Donnell said. "The problem with me is I can't put the two things together. This is an adult person, a little person ... it's so hard for me."
Handler takes the opposite view.
"I love little people," she said. "I want to tackle them. I see them and I want to hold myself down. I bite Chuy [Bravo] sometimes. ... He's so cute and that's my ultimate body. If you're going to have a little person, I want that shape, the corpulence."
Both Handler and O'Donnell's comments are a big issue for Little People of America, a support group for Americans of short stature due to dwarfism.
Spokeswoman Leah Smith says both viewpoints are equally offensive, but in different ways, so the group has taken the steps of sending separate open letters to Handler and O'Donnell to make their concerns known.
"We decided to separate the two because they are both equally offensive, but separate," Smith told HuffPost Weird News. "Handler used a lot of 'pity rhetoric' when discussing Chuy, saying he couldn't get a job if not for her.
"For the record, we're not in need of 'getting saved.' We are capable of being successful in any job."
Although Handler often asks Bravo to do things like dress up in baby clothes, he has publicly said he has no problems with that, saying it's part of the job. For that reason, Smith said the LPA has no problems with him choosing to take the job.
LPA has a bigger problem with O'Donnell's comments, because she attributes her feelings to heredity."My Nana was afraid of the 'Wizard Of Oz' munchkins," she told Handler.
Smith says the comedian is perpetuating "fear-based attitudes."
"Instead of pepetuating these fears, let's learn how to accept differences," Smith said.
The Huffington Post contacted representatives for both Handler and O'Donnell, but neither have responded the Little People of America's comments.
Smith said the group is angry, but doesn't plan a boycott of either performer.
"We'd rather start a discussion and deal with the issue head on," she said. "No other group is marginalized like this."
Handler and O'Donnell's comments come at a very important time for little people rights.
On one hand, actor Peter Dinklage is winning awards for his work on the HBO series "Game Of Thrones."
On the other hand, there is the case of Martin Henderson, a British dwarf who claims he was partially paralyzed on his birthday when a stranger lifted and heaved him onto the hard ground outside an English pub.
"Peter Dinklage made him a hot topic when he mentioned him [Henderson] in his Golden Globes acceptance speech, but it remains to be seen whether he will be our Rosa Parks."