Exploring themes and issues including happiness, personal fulfillment, spirituality and conscious living, guests who have appeared include: Elie Wiesel, Maya Angelou, Brené Brown, India Arie, Wayne Dyer, Gary Zukav, Iyanla Vanzant, Marianne Williamson, Phil Jackson, Ram Dass, Eckhart Tolle, Diana Nyad, Sarah Ban Breathnach, and Thích Nhất Hạnh.

[1] New conversations recorded exclusively for the podcast have featured such guests as: Reese Witherspoon, Mindy Kaling, Jimmy Kimmel, Amy Schumer, Phil McGraw, Will.i.am, Maria Shriver, former mayor of New Orleans Mitch Landrieu, Ralph Lauren, Tina Turner, Julia Roberts, and Michelle Obama.

The show was hosted by Jessica Williams and Phoebe Robinson of 2 Dope Queens and featured interviews with Jordan Peele, Stephen Colbert, Salma Hayek Pinault, Trevor Noah, Lin-Manuel Miranda, and Yara Shahidi.

On February 8, 2019, Winfrey hosted Oprah's SuperSoul Conversations from Times Square, another live show for the podcast and television series at PlayStation Theater in New York City.

[3] Season one episodes included interviews with Andra Day, Chip and Joanna Gaines, Priyanka Chopra Jonas, Sharon Stone, Jon Meacham, Dr. Bruce Perry, and Julianna Margulies.