Born in Montana, Gladstone spent her formative years on the Blackfeet Indian Reservation and later near Seattle, Washington. She went on to graduate with high honors from the University of Montana in 2008, earning a Bachelor of Fine Arts degree in Acting/Directing and a minor in Native American Studies.
Gladstone's early exposure to the public came through her role in Alex and Andrew Smith's adaptation of Winter in the Blood, a New York Times bestseller and influential novel by Blackfeet/Gros Ventre author James Welch.
Her breakout performance came in 2016 through Kelly Reichardt's Certain Women, a role that earned her numerous accolades, including the Los Angeles Film Critics Association Award for Best Supporting Actress, the Boston Society of Film Critics Award for Best Supporting Actress, as well as nominations for the Independent Spirit Award for Best Supporting Female and the Gotham Independent Film Award for Breakthrough Actor.
In 2017, Gladstone joined the esteemed Oregon Shakespeare Festival acting company, and in 2020, she starred in the Yale Repertory Theater production of Mary Kathryn Nagle's Manahatta.
In 2019, Gladstone reunited with Reichardt for First Cow, a film that went on to win the Best Film award at the 2020 New York Film Critics Circle Awards and was named one of the ten best films of 2020 by the National Board of Review.