The show originated from a pilot called 'Diseasy Does It' for a different planned series, Kenny and the Chimp, produced by Hanna-Barbera, which featured a group of rebellious children called 'Those Kids Next Door' as recurring characters.

The show was originally titled The Kids Next Door, but the name was changed to Codename: Kids Next Door after another network began developing an unrelated show called Pigs Next Door.

The pilot episode 'No P in the OOL' premiered in mid-2001 as part of Cartoon Network's The Big Pick II special, where viewers voted among 11 pilots to decide which would become a full series; it won and Kenny and the Chimp was not picked up.

The character Professor XXXL, who originally appeared in the 'Kenny and the Chimp' pilot 'Diseasy Does It', became a recurring villain in Codename: Kids Next Door, while Kenny and his chimp made a cameo appearance in 'No P in the OOL'.

Villains Mr. John Wink and Mr. Timothy Fibb are a parody of Mr. Wint and Mr. Kidd from the James Bond franchise and address each other in the same distinctive manner.

The villain Laura Limpin, also known as The Big Badolescent, is a parody of the Hulk, transforming into a hulking monster when angered.

Villains Robin Food and Little Juan are parodies of Robin Hood and Little John, stealing food from a retirement home cafeteria.

The episode 'Operation: A.R.C.H.I.V.E.', written by Mr. Warburton and Mo Willems, won the Best Television Series for Children Award at the 2005 Ottawa International Animation Festival.

After the series ended, creator Tom Warburton repeatedly pitched a sequel called Galactic Kids Next Door to Cartoon Network executives, and when he received no response, he wrote a script and produced a fan-distributed animatic-style pitch released online in March 2015, followed by a fan petition on Change.org signed by Warburton and voice actor Dee Bradley Baker.

In 2025, Warburton and the main cast voice actors held a live table read of a 'pitch script' for the Galactic Kids Next Door project at Nostalgia Con in Houston, Texas, as part of ongoing efforts to interest Warner Bros. in a revival.