Gillan made her transition to Hollywood starring in the horror film Oculus (2013), and played the lead in the ABC sitcom Selfie (2014).

[9][10] Gillan undertook a two-year stint as a member of the ensemble cast of the sketch comedy series The Kevin Bishop Show, in which she played multiple characters including celebrities such as Katy Perry and Angelina Jolie.

Part of the BBC's multimedia "switch" programming, the short episodes interconnect with online games that further explore the environments presented in the series.

[7] She made her first on-screen appearance as Amy in "The Eleventh Hour" with her cousin Caitlin Blackwood portraying a younger version of the same character.

[18] After making an appearance in Outcast, it was announced that Karen Gillan would star in an indie Scottish romantic comedy called Not Another Happy Ending alongside Emun Elliott in August 2011.

[19] She was selected by director John McKay because he came to know her during the production of We'll Take Manhattan, which he also directed, as "a very bubbly, vibrant, energetic, funny, slightly clumsy person" who was a perfect fit for the character.

[21] Karen Gillan told journalists that she was happy to be involved in a Scottish production that "isn't about drug use or fighting the English".

[43][44][45] In May 2013, Karen Gillan was cast as Nebula in the Marvel superhero science fiction film Guardians of the Galaxy,[46] which was released in August 2014.

[48] In May 2014, Karen Gillan was cast in the Western film In a Valley of Violence directed by Ti West, opposite John Travolta, Ethan Hawke and Taissa Farmiga.

[50] In 2015, Gillan had a bit part in the drama film The Big Short directed by Adam McKay, alongside Brad Pitt, Christian Bale, Ryan Gosling, Steve Carell and Melissa Leo.

[56][57] On 2 November 2016, it was announced that Gillan would write, direct and star in her directorial feature film debut with Burbank-based development and production company Mt.

2, this time becoming a member of the film's eponymous team,[62] and co-starred in The Circle, alongside Emma Watson, Tom Hanks, and John Boyega.

[69] The following year, she starred in the action film Gunpowder Milkshake alongside Lena Headey, Angela Bassett, Carla Gugino, Michelle Yeoh and Paul Giamatti.

[79] Critic consensus from review aggregator Rotten Tomatoes described the movie as "well-led", and John DeFore for The Hollywood Reporter said that "Karen Gillan, who has spent much of her post-Doctor Who decade playing cyborgs, computer avatars and a thinly imagined assassin, has a barely more human role to play here; to the extent that she makes either Sarah worth rooting for, it's an achievement.

Better received was the ITVX comedy drama series Douglas Is Cancelled, which was released in June 2024 and marked Gillan's return to British television.

"[88] Gillan appeared in The Life of Chuck, reuniting with filmmaker Mike Flanagan, with whom she last collaborated on Oculus,[89] which premiered in September 2024 at TIFF.

[91] In 2011, Gillan helped promote Fashion Targets Breast Cancer (FTBC)[92] and the opening of Squirrel Ward at the Great Ormond Street Hospital in London.

The film is about the high suicide rate in the Scottish Highlands, and Gillan made a public pledge to support the mental health charity.

[97][98] In May 2022, Gillan married Nick Kocher, an American comedian of the sketch duo BriTANicK, in a ceremony at Castle Toward in Dunoon, Scotland.