A backup segment, a remake of Hanna-Barbera's Secret Squirrel (entitled Super Secret Secret Squirrel), was shown in between the main 2 Stupid Dogs cartoons in many of the 13 episodes, similar to early Hanna-Barbera cartoons in the 1960s.
2 Stupid Dogs is about a big dog and a little dog, who aren't very smart as the title explains, and their everyday misadventures, with an animation style unusual for the time: a very flat, simplistic style similar to early Hanna-Barbera cartoons of the '50s and '60s, but with early '90s humor and sensibility. In addition, the Big Dog talks much less than the Little Dog does and most of the time, the Big Dog talks about food. It also did not have a series structure, similar to many humorous cartoons and sitcoms. The show did not follow a continuous storyline — what happens in one episode has little to no effect on another. 2 Stupid Dogs contained very brief sexual innuendos, as did other cartoons at the time, such as Rocko's Modern Life.
2 Stupid Dogs was the beginning of the successful revival of Hanna-Barbera's fortunes, since the studio had not launched a bona fide hit since The Smurfs in 1981. The Turner Entertainment president installed MTV and Nickelodeon branding veteran Fred Seibert as the head of production. Seibert's plan to reinvent the studio was to put his faith in the talent community, a first for television animation, and Hanna-Barbera in particular. His first pitch and first series put into production in 1992 was 2 Stupid Dogs, by recent California Institute of the Arts graduate Donovan Cook. Ren & Stimpy creator John Kricfalusi was credited to adding "tidbits of poor taste" to the three Little Red Riding Hood episodes, and a few other Spümcø artists also contributed to selected episodes during the course of the show (there were a few passing references to Ren & Stimpy over the course of the series as well).
Several artists and directors from the show became the first creators in Seibert's What a Cartoon! program; 48 short, original character cartoons, made expressly for the Cartoon Network, and designed to find the talent and hits of the new generations. Larry Huber, who later served as executive producer on the What a Cartoon! program, teamed first with Seibert as producer on the 2 Stupid Dogs series and directed the middle cartoon, Super Secret Secret Squirrel. 2 Stupid Dogs eventually helped launch the careers of creators Genndy Tartakovsky (Dexter's Laboratory, Samurai Jack, Star Wars: Clone Wars and Sym-Bionic Titan), Craig McCracken (The Powerpuff Girls, Foster's Home for Imaginary Friends, and Wander Over Yonder), Butch Hartman (Fairly Odd Parents, Danny Phantom, T.U.F.F. Puppy, and Bunsen Is a Beast) Miles Thompson, Paul Rudish, Rob Renzetti and Zac Moncrief.
- Big Dog - He is a large grey Old English Sheepdog with a purple nose. (In an episode where they were in a farm, he was even able to herd sheep.) He is much stronger than the Little Dog. Big Dog is generally too lazy to bother with anything, and most of the time seemed more aloof and unconcerned about his surroundings than actually stupid. In some episodes, he surprisingly reveals deep philosophical intelligence. A running gag about Big Dog is he would spit out a whole cob of corn he ate.
- Little Dog - He is a small brown Dachshund. Little Dog is much more energetic and hyperactive than Big Dog. Little Dog is completely scared by cats (possibly a case of ailurophobia), and when a cat appeared, it was Big Dog that had to scare the cat away. He does know a little about history (such as when in "Substitute Teacher", an Abraham Lincoln parody was played, when the Lincoln actor (Mr. Hollywood) dies from a sword strike, the little dog remarks "I thought Lincoln was shot"). He often refers to things he doesn't like as "caca!" In one episode, Sheep Dog, it was revealed he didn't know his own name. When he asked Big Dog about it and got "I don't know" as reply, he wrote "Ida Know" on the form.
- Kenny Fowler - A small skinny kid with nerdy glasses, who is often pushed around by other kids, and often asks the dogs for help, in a certain episode where he tries to talk to Buffy and gets nervous. He has a bully who often taunts him by saying "What a Fowler!"
- Hollywood - A large man who likes to point out others' mistakes, always in the same unnecessary fashion; he will begin by saying, in an admiring tone "Well, isn't that cute?" and then shout at the top of his lungs "But it's wrong!" - always accompanied by the background sound of a striking foghorn. At the one occasion where he says "Well isn't that cute?" without adding "But it's wrong!", he breaks the fourth wall by telling the viewers they probably expected him to shout that. Whenever the dogs bump into Mr. H (the way he introduced himself as when he was a teacher) he has a completely new appearance and on one occasion is a woman. He has also had many occupations such as a teacher, farmer, Noah, casino manager and pet shop owner. In "Pie in the Sky" he assumes multiple shop owners of a retail store, and at the end, all of his guises are in the same scene together at once.
- Cubby - A fat spotty teenager with big glasses, blonde hair and blue lips. In the episodes he appears in he assumes the role of a different job, like Mr. Hollywood, such as in the episode "Far-Out Friday" he is a clerk at the supermarket. In the episode "At The Drive-In" he is the attendant at the snack bar. He has a squeaky voice and often lets off gas when excited i.e. "Post Office". He helps the stupid dogs with questions and problems they have which mainly involves food.
- Buffy Ziegenhagen - A girl in Kenny's class that he has a crush on, and who has a secret crush on him.
- Red - A parody of Little Red Riding Hood, she's a small, meek little girl that the Dogs often encounter. When she speaks, she shouts one word in the sentence very loudly compared to the quiet tone of voice she usually has. The Dogs usually just join her for food. She needs glasses and even with them her sight is far from 20/20 (which some viewers see as a logical explanation for why Red can't see through Big Bad Wolf's granny disguise—the Dogs are simply stupid). In her first appearance, Red mistakes Big Dog for Granny and Little Dog convinces him to play along for her cake. They miss Granny's home and end up at the Three Bears home. At her next appearance, they once again miss Granny's home and instead go to the gingerbread house, where the witch, not wanting to wait for Hansel and Gretel, decides to eat Red. In her third appearance, Red and the Dogs do reach Granny's but just because Big Bad Wolf got tired of waiting and dragged them there.
Super Secret Secret Squirrel
Secret Squirrel and Morocco Mole were revived in 1993 for back-up segments of TBS Superstation's animated series 2 Stupid Dogs. Titled Super Secret Secret Squirrel, these new cartoons featured Secret Squirrel voiced by Jess Harnell imitating Mel Blanc and Morocco Mole voiced by Jim Cummings.
These segments featured different artwork compared to the original 1960s cartoons. All the characters inhabiting the world were now animals. Double-Q, called simply the 'Chief' in these shorts and voiced by Tony Jay, is a cape buffalo instead of a man with a balding hairline, and arch-foe Yellow Pinkie was replaced with a sea lion known as Goldflipper (voiced by Jim Cummings). These new shorts also introduced Penny (voiced by Grey DeLisle), a female squirrel assistant to the Chief (à la Miss Moneypenny) as a possible love interest for Secret (as hinted at in the episodes Queen Bea and Quark). Morocco's color scheme has been redesigned, wears sunglasses, and has an evil twin brother, Scirocco Mole (voiced by Jess Harnell). Secret's art design remained relatively intact, but with a more modern design than the previous animated series' version of the character. His hat has a slightly different style. This new series seems to have fallen under the villain of the week formula and Secret Squirrel and Morocco Mole have once appeared on a 2 Stupid Dogs story.