Dr. Drakken, also known as Drew Lipsky, is Kim's arch-nemesis and has appeared in more episodes than any other villain. His primary goal is almost always world domination, but he often devises overly complicated plans to do so. His latest plan usually involves typical villain devices like death rays, killer robots, and various obscure technological advanced devices. He operates with no henchmen and his one sidekick, Shego, because of his financial troubles, and everyone seems to know about his "secret" lairs. His transformation to an evil villain was largely due to teasing from his ex-best-friends, Mr. Dr. Possible, and Professors Chen and Ramesh.
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Shego is Kim's most formidable enemy, being the smartest and the most dangerous of all the villains. Still, she remains a sidekick to Drakken, even after a consistent streak of world domination failures on Drakken's part, but she does get most of her fun from making sarcastic remarks towards Drakken and battling Kim Possible. Her martial arts skills are similar to Kim's, and she can fire glowing green plasma from her hands. She previously worked as a superhero with her four brothers - Hego, Mego, Wego, and Wego - but their behavior irritated her so much that she switched the evil side. She has a softer side, which is the key to her possibly becoming good again.
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Duff Killigan is a Scotsman known as a "rogue golfer" because he uses his woods and irons to hit exploding golf balls at his enemies. He can also use his golf clubs to club people, if you'll excuse the pun. His dream was once to cover the world with rapidly growing grass in order to create an enormous golf course.
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Lord Monkey Fist, also known as Lord Montgomery Fisk, is an English nobleman who spent his family fortune getting his hands and feet surgically altered into ape appendages. He frequently boasts his skills in a type of monkey kung-fu, and he fights alongside his team of trained monkey ninjas (chimps with martial arts skills).
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Senor Senior, Junior, usually known as Junior, is the son of retired billionaire Senor Senior, Senior. Although his father constantly tries to encourage him to devise evil plans, Junior is more interested in fashion and suntanning. Years of being spoiled has made him rather unskilled physically, despite his large build, and he's not very bright either.
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Professor Dementor is Dr. Drakken's rival, and he's a much more successful mad scientist than Drakken, thanks to his well-financed team of skilled henchmen and his ability to build functional doomsday devices. He speaks with a European accent, possibly German, and he has a short stature.
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Gill is the name that a boy adopted after he fell victim to a mutation after spending too much time swimming in the lake at Camp Wannawepp. Before the mutation, he was known as Gil (with one "l") Moss. Gil blames Ron for his mutation because of a switch in camp activities after Ron voiced his suspicions about the lake. His abilities include shooting toxic muck from his mouth. (He has appeared in 2 episodes.)
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DNAmy is a geneticist whose unethical practices led to her disgrace. She's obsessed with Cuddle Buddies, which are Beanie-Baby-like toys that are each a cross between two different animals. This obsession inspired her to create mutant crosses between completely different animals. She was the one who gave Monkey Fist his ape hands and feet.
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The Knights of Rodeghan hold a centuries-old grudge against the royal family, and this grudge has been passed down to the modern knights, who use modern technology to try to eliminate the royal family. (They have appeared in 1 episode.)
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Jackie the Jackal is Jack, an announcer at the pro-wrestling games whose desire to become a competent wrestler drove him to use an ancient Egyptian artifact to become a strong jackal. (He has appeared in 1 episode.)
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Adrena-Lynn is a stunt show performer who fakes her stunts. When Ron discovered and exposed this secret, Adrena-Lynn sought revenge on Ron and Kim. (She has appeared in 1 episode.)
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Frugal Lucre is an employee at discount store, Smarty Mart, who used an expired barcode to attempt to bring down computer systems and, supposedly, the entire Internet. (He has appeared in 1 episode.)
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Senor Senior, Senior is a retired billionaire who became a villain as a hobby when Ron mistakenly suggested it. He is extremely well-mannered and eloquent, and he believes strongly in "the code of villainy", which contains rules like leaving your opponents alone after tying them to a doomsday device. He's always trying to get his son to become a competent villain, and he's also a skilled X-Games stunt master.
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Motor Ed is a mechanical expert who loves using his expertise to beef up cars and use them for somewhat evil purposes. Motor Ed cares so much about his mullet that he quit his original job as a scientist because he refused to adhere to the dress code. He also happens to be Dr. Drakken's cousin. (He has appeared in 2 episodes.)
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Aviarious is a bird-like villain who lives in Go City. Subsequently, he is the primary foe of Team Go, which used to consist of Shego and her brothers - Hego, Mego, Wego, and Wego. A giant condor carries out all attacks for Aviarious. (He has appeared in 1 episode.)
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Commodore Puddles is Dr. Drakken's pet poodle. Puddles was displayed as an uncontrollable violent dog in one episode, but he looked mostly gentle and harmless in another, where he was accidentally zapped into a giant dog. (He has appeared in 2 episodes.)
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The mutant Snowmen are snowmen who came to life because the snow that composed these snowmen supposedly came from a toxic lake. They are capable of creating more snowmen like themselves, and they'll break into stores to make sure each snowman has a pipe, a hat, and all the other standard snowmen apparel. (They have appeared in 1 episode.)
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The Killer Bebes, usually just known as The Bebes, are robots created by Dr. Drakken. They were designed to follow Drakken's orders, but once they realized that Drakken was not a "perfect" being fit for rule, they decided to rule themselves. (They have appeared in 2 episodes.)
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Bartholomew Lipsky is Dr. Drakken's (Drew Lipsky's) ancestor, who also attempted world domination. His sidekick was coincidentially Shego's ancestor, Miss Go. (He has appeared in 1 episode.)
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Miss Go is Shego's ancestor, who aided Dr. Drakken's ancestor, Bartholomew Lipsky. (She has appeared in 1 episode.)
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White Stripe is an actor who played a skunk villain on the show, The Fearless Ferret. He mistakenly believed that this show was reality, which led him to think that he was a real villain. (He has appeared in 1 episode.)
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Jack Hench supplies expensive villain services like elite henchmen and villain technology to many customers, including Professor Dementor.
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Gemini, whose real name is Sheldon, is an enemy of Global Justice, headed by his twin sister. His career as a villain seems to be solely to compete with his sister. (He has appeared in 1 episode.)
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Fukushima is a student of the Japanese secret ninja school that Ron briefly attended as an exchange student. He acted in a hostile manner towards Ron since the start of his stay. (He has appeared in 1 episode.)
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