Hugh, a stay-at-home dad specializing in the art of meatloaf, and Lila, one of the busiest executives ever, are the parents of Johnny, Susan, and Mary. Their parenting style is lax, and Mom and Dad have only one mandatory requirement: every night at 6 p.m. sharp, the whole family sits down for dinner and talks about the day. If the girls can't change Johnny back from a rampaging monster or return him from the future, they'll be grounded and banned from the lab for a week.
Dukey was the smelliest, mangiest, and friendliest mutt at the pound, and Johnny picked him to be his pet. Johnny's twin sisters genetically altered Dukey so he can talk, walk, and take a bath. Despite his uniquely human abilities, Dukey's still a dog who can't deny his natural dog urges. Johnny and his sisters strive to keep Dukey's power to speak a secret for two reasons: Mom and Dad have strictly forbidden DNA experiments in the house and Johnny worries if Dukey is found out, he'll lose him.
Two buff and tough federal agents, Mr. Black and Mr. White work for the SSGA (Super Secret Government Agency). But their big secret is that they realize that Johnny and Dukey, along with the girls, are far more capable of crushing any evil that foists itself on Porkbelly than they are. A quid-pro-quo friendship underlies all the madness, and the six actually have fun together.
Super-genius twins Susan and Mary are the only 13-year-olds in the doctorate program at the Porkbelly Mega Institute of Technology. They will win the Nobel Prize one day, but right now they're more interested in solving adolescent problems through science-and impressing the cute boy next door. As adults, they would be seen as mad, but as kids, they are merely curious. Be it a time machine, a brain chip, bionic prosthetics, or everlasting lip gloss, the twins always have a bribe ready for Johnny.
Super-exuberant and imaginative, 11-year-old Johnny Test has a zest for life and an ambition just one step behind his ability. He wants to drive monster trucks, hit homeruns, and be the smartest kid in class, plus walk on the moon, breathe underwater, and have superpowers. Luckily, he has genius twin sisters who allow him to live out his dreams-as long as he participates in their experiments. It's win-win, though Johnny rarely considers the repercussions of being their guinea pig.
Eugene is Porkbelly's resident evil genius who also tinkers in the sciences. He once attended the exclusive Mega Institute with the twins, but after an "unfortunate incident" that resulted in Professor Slopsink receiving a metal claw for a hand, Bling-Bling Boy was expelled. Eugene wants Susan to be his girlfriend, even if means destroying Porkbelly. His family is filthy rich, so Eugene can get all the materials he needs for his world-threatening inventions.
Gil is the all-star jock next-door neighbour. Susan and Mary are sooooooo in love with him, and many times they invent stuff simply to get closer to him. But it always backfires. Gil, who has become somewhat bored being super-popular and handsome, finds Johnny to be pretty cool for an 11-year-old and treats him like his little brother.