[18][19][20] One of her first acting experiences as a child was when Missoula Children's Theatre came to her East Glacier, Montana, hometown and cast her as an evil step-sister in Cinderella.

[22] In 2008 she graduated from the University of Montana with a Bachelor of Fine Arts (BFA) in Acting/Directing and a Native American Studies minor.

She taught an image theatre acting method she called a "sculpture garden" as violence prevention sponsored by the National Indigenous Women's Resource Center.

She then acted in Winter in the Blood (2012) and Buster's Mal Heart (2016) before making her career breakthrough as Jamie, a rancher, in Kelly Reichardt's film Certain Women (2016).

[28][29] Gladstone performed the role of Kate Keller in the 2014 Montana Repertory Theatre's national touring production of The Miracle Worker.

Gladstone was in the Oregon Shakespeare Festival acting company in 2017 and starred in the Yale Repertory Theatre production of Mary Kathryn Nagle's Manahatta in 2020.

[32] Gladstone was cast in the lead role of Mollie Kyle in Martin Scorsese's 2023 feature film Killers of the Flower Moon, which was released theatrically in October 2023.

[40] Earlier in 2023, Gladstone starred in Fancy Dance which premiered at the 2023 Sundance Film Festival to critical acclaim and was distributed worldwide by Apple TV+.

[43] Her performance earned her a nomination for the Primetime Emmy Award for Outstanding Supporting Actress in a Limited or Anthology Series or Movie.