"Two Stupid Dogs" follows the lives of two dogs: the overly excited Little Dog (the dachshund) and easy-paced Big Dog (the sheepdog). These crazy canines don't know how to fit in the world, and they definitely don't have any know-how. They often find themselves in commonplace situations (going to the drive-in, walking through the mall, working on the farm), some not so common situations (stuck on a space shuttle, a contestant on a game show, getting mistaken for the prime minister) and even in some familiar situations (little red riding hood, Noah's ark, and Hanzel and Gretel). But no matter the situation, their stupidity usually leads them to calamitous results.
Pierce The Little Dog (voiced by Mark Schiff), a small tawny-colored dachshund, is much more energetic and hyperactive than Zeke. Pierce is completely scared by cats, and when a cat (the very same cat) appears, it is Zeke who scares the cat away. He often refers to things he doesn't like as caca!.
Zeke The Big Dog (voiced by Brad Garrett) is a large grey Old English Sheepdog with a purple nose. He is much stronger and significantly more stoic and reserved than Pierce, and speaks much less - on occasion he has also been shown to be surprisingly wise.
The Cat is a small innocent cat which Pierce is terrified of, despite its being harmless. Zeke's bark causes the Cat to freeze in terror; however, the Cat is not afraid of Zeke unless he barks.
Mr. Hollywood (voiced by Brian Cummings) is a large man who likes to point out others' mistakes. Whenever the dogs bump into him, he has a completely new appearance. He has also had many occupations such as a teacher, farmer, casino manager, Noah and pet shop owner. When pointing out others' mistakes he will say, "Aww, isn't that cute? BUT IT'S WRONG!!!" or, in the event that others (usually the dogs) repeat their mistakes, "Aww, isn't that cute? BUT IT'S STILL WRONG!!!"
Kenny Fowler (voiced by Jarrett Lennon) is a small skinny kid with nerdy glasses, who is often pushed around by school bully Buzz and often asks the dogs for help. He often falls down on the floor.
Cubby (voiced by Rob Paulsen) is a fat, spotty man 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.
Buffy Ziegenhagen (voiced by Tawni Tamietti) is a girl in Kenny's class that he has a crush on and who has a secret crush on him.
Red (voiced by Candi Milo) is a small, meek little girl that the dogs often encounter. When she speaks, she shouts one word (sometimes two) in the sentence very loudly compared to the quiet tone of voice she usually has.
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