The series also featured many well-known guest stars such as Mark Hamill, Slash, Kendall Jenner, Jim Parsons, Carly Rae Jepsen, Carlos Alazraqui, Jim Belushi, Matt Bomer, "Weird Al" Yankovic, Rainn Wilson, Seth Green, George Takei, among others.

A reoccurring character from the Annoying Orange YouTube series called Nerville (played by internet personality Toby Turner) now runs the supermarket (mainly as the janitor), and is the only human who can talk to the fruit.

Boedigheimer confirmed that they had started producing a TV series based on Annoying Orange in April 2010.

[9] When Boedigheimer began filming the pilot episode of the TV show in February 2011, they discussed with Cartoon Network about airing it on the station,[10] which was picked up on November 18 of that year.

[20][21][22] Most of the visual effects, compositing, off-line, on-line, audio, RED Camera footage, graphics, and animation were done at Kappa Studios in Burbank, California.