These are characters who are against the main cast and the most of the minor characters in Happy Tree Friends. Almost all of them are involved in killing somebody.
For the sake of this list, an antagonist is defined as: a character or a group of characters which stand in opposition to the protagonist or the main character. Do not add anyone who does not meet this definition.
- Main article: Fliqpy
Fliqpy is the main antagonist of the show and the most violent character out of all. He is the evil side of Flippy and will emerge whenever he confronts or hears something that reminds him of war. He is a murderous individual who has caused a lot of the deaths on the show and often kills other characters in such creative yet brutal ways.
Though they don't typically intentionally kill other characters, they act as Antagonist to nearly characters but each other in almost all episodes they appear by stealing from them.
- Main article: Mr. Pickels
To this day, his existence in the reality of the show is under debate but either way, he is definitely an antagonist. He is Lammy's debatably imaginary friend. If he's an actual living character, he intentionally kills any character, living or otherwise (such as ripping off the head of Petunia's teddy bear or stabbing a sock puppet), who tries get close to Lammy then frames her for the murders. If imaginary, then the idea of him tricks Lammy into killing her friends which still qualifies him as a antagonist.
- Main article: The Cursed Idol
A Mayan statue which brings death and bad luck. It does nothing else other than just sit there while bringing death and bad luck. When it appears, everyone who is near the statue dies brutally. This idol is based on the golden fertility idol in Raiders of the Lost Ark. It features in the episodes Treasure Those Idol Moments, Hello Dolly, and Idol Curiosity. It appears as a prop in many other episodes such as Crazy Ant-ics, Happy Trails Pt. 1, Milkin' It, Class Act, Ipso Fatso, Who's to Flame? and Every Litter Bit Hurts.
- Main article: The Demon
It made it's first and only appearance in Read 'em and Weep. It appeared when Pop reads from a satanic book similar to the Necronomicon. It appears to based on the demon Pazuzu from The Exorcist (the Demon's head was not shown, though its tentacles were visible). It is possible that it could be a variation on Cthulhu, a monster created by H.P. Lovecraft, however the Cthulhu is too big to fit inside Cub or Lumpy.
- Main article: The Ants
Whenever they appear in an episode, it will always involve Sniffles trying to eat them, only for him to be tortured and killed by The Ants in the most sadistic manners. Due to them torturing Sniffles, they are (Debatably) considered the most hated and despised characters of Happy Tree Friends. They are voiced by Kenn Navarro, Warren Graff and Ken Pontac.
- Main article: Generic Tree Ninjas
A special group of Generic Tree Friends from Japan, who terrorize the sacred places where Buddhist Monkey lives. These dark ninja are exclusive to the Buddhist Monkey episodes, Enter the Garden, Books of Fury, and Three Courses of Death (excluding the episode Keepin' it Reel where the ninjas appear on a movie screen). In Enter the Garden, the ninjas wear green outfits with a leaf on their chest, while in "Books of Fury", they wear brown outfits with an open book on their chest.
The evil leader of the tiger soldiers with a metal claw in place of his left hand and a monocle on his left eye. He first appeared in Operation: Tiger Bomb. Durning the war, he and his army are the main enemies of both sides of Flippy and his allies Sneaky and Mouse Ka-Boom.
They are led by the Tiger General.
- Main article: The Rat
He has appeared only in the episode Mole in the City. He appears to be the arch-enemy of The Mole, seeing as they are both involved in Industrial Espionage. He was killed by explosives that The Mole planted in a briefcase. His death may have been permanent.
Giant Lumpy (played by Lumpy) as he is seen in Dunce Upon a Time, is a giant who lives in a castle in the sky and is loosely based on the giant in Jack and the Beanstalk. He is portrayed as a villain, eating the normal sized characters and brutally killing them when they escape. He also kidnaps Petunia as a slave princess to spin straw into gold for him. When Giggles sees Lumpy killing some of the other characters, she tries to save them. Unfortunately, they end up dying in even worse ways than they would have if they had remained in their jars. Giggles kills Giant Lumpy by cutting down the beanstalk while he was climbing down it. He fell to his death, where he lay like a bridge across a valley. A piece of his castle then comes down and crushes him in half, as well as killing Lifty & Shifty.
Vampire Lumpy (played by Lumpy) as he is seen in All In Vein. He spots Giggles in his fridge. he hypnotizes her, and sucks her blood with a straw. Unfortunately, he is disgusted by the taste and wastes the blood and kills her, then he attempts to kill The Mole but he kills himself due to his blindness and Vampire Lumpy ends up getting hit by a train. He is later in a ambulance with numerous blood bags, and drinks all of them. Toothy checks the back of the ambulance, only to run away realizing Lumpy was a vampire. He is later killed by the sunrise due to not being able to move, and later his skull impales Toothy.
- Main article: The Dark Shadow Lord
An unknown antagonist in the shadows is the evil master who sent the Generic Tree Ninjas to attack Buddhist Monkey. He also sent Char Sui to kill Buddhist Monkey. He watches over Buddhist Monkey in his magic cauldron.
- Main article: Char Sui
Char Sui is one of The Dark Shadow Lord's assassins sent to eliminate Buddhist Monkey. However, he failed and got killed by Buddhist Monkey in Three Courses of Death. He owns a giant purple crab he used in his efforts to kill Buddhist Monkey, but the both of them got boiled by his fire-summoning technique.
- Main article: Splendont
Splendont is a rival super hero of Splendid. He was trapped in a mirror floating in space that broke when a rock went up and hit it. He is likely to return in the future Splendid's SSSSSuper Squad episodes.