When Ross asked Witherspoon which role in her career "changed" her the most, Witherspoon named "Wild."
"I had hypnosis, I was so scared," she recalled. "I was having panic attacks for three weeks before I started."
"There was the nudity, sexuality, and drug-use aspect, but also being alone on camera with no other actors," she continued. "I hadn't ever been alone in scenes for days and days. There were probably 25 days of the shoot where I had no other actor opposite me. It was just me and a camera and a backpack. I was like, 'Is this going to be so boring?'"
The "Legally Blonde" star then shared what inspired her to want to make a movie based on Cheryl Strayed's memoir.
"Cheryl Strayed's book was so beautiful and sacred to me because it spoke to me so deeply about how we as women have to save ourselves," she said. "There's no mother or father coming to save us. There's no spouse. I thought it was radical that at the end of the film, she ends up with no family, no money, no job, no partner, and she's happy."
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Witherspoon -- who portrayed Strayed in the film -- went on to receive a Best Actress Oscar nomination for her performance. She also produced the project through her production company.
"I don't know if I'll ever work that hard again," Witherspoon told Ross, "but it changed me on a cellular level."
Meanwhile, the "Walk the Line" actress later noted that she had been "crying a lot" during the week in which the interview was conducted.
"My gosh, I've been crying a lot this week," Witherspoon said after Ross asked her opinion on tears. "I'll have memories of my kids when they were little, or I'll remember my favorite English teacher from high school, and I'll just burst into tears."
The "Big Little Lies" star shares daughter Ava, 21, and son Deacon, 17, with ex-husband Ryan Phillipe. She also has an 8-year-old son, Tennessee, with her husband Jim Toth.
During her Q&A with Ross, Witherspoon opened up about "the idea of having a long relationship" with her children as she does with her own mother.
"That makes me want to cry, the idea of having a long relationship with adult children," she explained. "I never expected the kind of relationship that I have with them, but it's so rewarding to be able to have kids that you can process life with a little bit, and they help me understand the complexities of what it means to be a human now. So I'm really, really grateful that these little humans are in my life. Adult humans. I have two adult children now, Tracee. It's crazy."