"I feel good. I wouldn't have said yes to coming back if I didn't," she told ABC News backstage after the show. "They asked me a year ago, 'Would you consider [coming back]?' ... The concept of being able to do this show in a way that celebrates and elevates women is hard for me to resist."
"The fact that I look so different has been difficult and unexpected," she said. "Everyone assumes that obese people would just be jumping for joy that they were healthier and thinner and able to fit into store-bought sizes, we don't have to go to the plus store. But it's also filled with a lot of emotional turbulence, you wouldn't expect."
O'Donnell added that she is addressing the change in the right ways and getting support from other people in similar situations.
"I have a group that I go to, where women talk about how they feel," she said. "A lot of marriages break up once one person gets healthy. Luckily, my wife is very healthy, always been healthy, loves me and encourages me to be healthy."
"When we decided to get married, she said, 'But I want 40 more years and I don't want you to die on me, so you need to do something for your health,'" she added.
But O'Donnell didn't take her wife's request seriously until Rounds got cancer.
"The stress of that as well as being as big as I was, as well as being so depleted in every way, I had a massive heart attack," she said of the 2012 scare that almost took her life. "So, since then, I can't ignore it anymore. It's not like I don't want the cupcake that I saw, I just know that that's not a good choice."
O'Donnell also touched on how she "wasn't in the best place" last time she hosted the show, since she was going through a divorce from ex Kelli Carpenter in 2007.
The host, who was welcomed back to the show via a standing ovation on Monday, said her baby has only kept her up two nights in the past year and a half, which worries O'Donnell, because her wife thinks that's normal.
"She keeps going, 'We should have another one!'" she said, laughing. "So, I'm happy, I'm in a good place."