[8][9][10] Guillén has appeared in recurring roles on television series such as Alistair Delgado on Huge (2010), Cousin Blobbin on The Thundermans (2013–2018), George Reyes in Eye Candy (2015), and Benedict Fenwick on The Magicians (2017–2018).

[12] Beginning in 2019, Guillén played the role of Guillermo de la Cruz, the vampires' human familiar, in the FX television series What We Do in the Shadows.

[13] He also appeared in Quibi's science fiction drama series Don't Look Deeper,[14] before the platform shut down in December 2020.

[15] Hank Steuver, in his review of What We Do in the Shadows in The Chicago Tribune, stated that Guillén "provides at least half the big laughs" in the show.

[17] In 2023, Guillén appeared on The Late Show with Stephen Colbert in a skit as Representative George Santos.