
Gotham City has a ton of villains, and these ones are the worst of the worst.
- Jerome Valeska, in his first appearance, ends up in Arkham Asylum for murdering his mother, in his words, for being a "nagging drunken whore". When interrogated, he laughs it off as if it were a joke. When he and several other inmates are recruited into the Maniax gang by Theo Galavan, Jerome functions as the de facto leader, announcing their presence by throwing several hostages off a roof. Later, he attempts to set a bus full of high school cheerleaders on fire; shoots up the GCPD station, personally killing Commissioner Essen; and kills one of his own men for cracking a joke he was about to make. Jerome later kills his father, then poses as a magician to hold a children's hospital charity hostage, killing the deputy mayor. He plans to kill thirteen-year-old Bruce Wayne, threatening his butler Alfred to draw him out. When he gets his hands on Bruce, he begins to slowly slit his throat in the following standoff. Following his death, Jerome had a cult that embraced his ideology. Shortly after his resurrection, Jerome has Dwight, the leader of said cult, strapped to a bomb as Jerome didn't like Dwight using Jerome's face when he thought the resurrection had failed, and announces his return to the city, encouraging his followers to spread death and chaos, then detonating the bomb. In the chaos, Jerome intends to finish killing Bruce, before deciding to do something special to kill him. Jerome takes Bruce to a sadistic theme park where innocent people are tortured and killed in twisted carnival games, forcing Bruce to watch and stapling his arm, before preparing the main event; to blast Bruce with a cannon in front of his followers. He takes over Arkham and teams up with Jervis Tetch and Jonathan Crane to form the Legion of Horribles, the latter of which he commissions to create the Joker Venom, before deciding to use it on Gotham and, when it fails, tells Gordon that his legacy will go on before killing himself. As a last act of evil, he delivers a package of Joker Venom to his twin brother Jeremiah, which turns him into Gotham's most infamous villain to carry on his brother's malevolent spirit. A maniacal psychopath who believes in chaos for the sake of chaos, Jerome was a criminal that has given Gotham scars like none other, and it was simply after just one bad day.
- Dr. Francis Dulmacher AKA the Dollmaker is soft spoken surgeon who works with rich clients and mastermind of human trafficking for the purpose of organ harvesting for his experiments. He takes them to his facility on a private island where he keeps them hostage with his hired thugs, who he'd often send to carry out his abductions. Early in the season, he sends two of his lackies to abduct street children to such a fate, using charity as a lure. When his plan is exposed and the children are sent into protective care, he tries to have his lackies hijack the convoy. Partway through the season, crime boss Fish Mooney finds herself in Dulmacher's clutches, he intends to take her eye, and later shows what happens to those who fail or cross him; he shows her his former lackies disasembled and reassembled with female parts.
- Professor Hugo Strange is the Big Bad of the latter half of Season 2. Originally partners with Thomas Wayne in the Pinewood Farms project, a project meant to find cures to afflicted citizens' illnesses, Strange took advantage of Wayne's trustfulness to perform horrifying experiments on the patients. When Wayne discovers Strange's actions and closes the project, Strange has him and his wife gunned down in front of their son, Bruce Wayne. Partnering with the Court of Owls, Strange becomes the head of Arkham Asylum, where he continues his torturous experiments on the defenseless patients, resulting in many of them going even more insane and being transformed into monstrous creatures, and, to keep said experiments under his thumb, Strange regularly subjects them to painful mental torture. Discovering the secret to bringing the dead back to life, Strange begins reviving dead criminals, all of which come back as raving lunatics who kill numerous innocents, which Strange happily assists them in while convincing them they are his "children". When Bruce Wayne and James Gordon continue to investigate him, Strange subjects them both to mentally stressful interrogations before trying to kill them, along with Selina Kyle, the latter for no reason other than annoyance. On the Court of Owls' orders, Strange tries to detonate a nuclear device that could possibly kill thousands of people, for no apparent reason other than fear for his own life. A cold sociopath who committed his atrocities simply to see if he could, Hugo Strange showed no concern for any of his victims, and is ultimately revealed to be responsible for nearly all of Gotham City's inevitable chaos with his monstrous experiments.
- Lazlo Valentin, AKA Professor Pyg, from season 4, is a sadistic hitman known for copying the MO of multiple serial killers. He arrives in Gotham and makes himself known to the GCPD by killing many of its cops in various brutal ways, which include slashing some with a cleaver; having one blown up by a grenade; and having many get shot by a machine gun. He later kills six homeless people, bakes them into meat pies, and forces the Gotham socialites to eat said pies. Upon being caught and sent to Arkham Asylum, he viciously kills an inmate for interrupting his music leisure, and kills multiple staff while escaping the Asylum. He then kills crime boss Carmine Falcone on Sofia Falcone's behest, and attempts to kill Commissioner James Gordon himself before Sofia shoots him.
- Jeremiah Valeska is the aforementioned Jerome's seemingly orderly twin brother and a powerful but suspicious businessman. According to Jerome, Jeremiah is just as bad as he is and plans to make him his heir; when seemingly Driven to Madness by a special gas, Jeremiah states it did nothing but alter his appearance, and that he intends to usurp Jerome's legacy to gratify his own ego; Jeremiah starts off with a plan to detonate powerful bombs all over Gotham, before incinerating his new followers after he fails, and has his lover Ecco shoot herself to prove her loyalty. Jeremiah later teams up with Ra's Al-Ghul to destroy all the bridges out of Gotham and turn the city into a lawless despot. Obsessed with Bruce Wayne, Jeremiah does anything to become the center of his world, including shooting Selina Kyle; torturing a decoy of Alfred to self-mutilate; attempting to recreate the night of the Wayne murders with brainwashed victims, before trying to use Jim and Leslie as a substitute; and attempting to unleash chemicals onto the city to ruin it beyond repair. Emerging as The Joker ten years later, Jeremiah eventually kills Ecco, stating they'll be others like her, before kidnapping and trying to drop Jim Gordon's young daughter into a vat of chemicals.