Recurring and guest
Darrell Brown as Perry White, the editor-in-chief of the Daily Planet and Lois, Clark, and Jimmy's boss.
Tyrannko, the prince of the reptilian Subterranosauri.
Krull, a Subterranosauri.
Zehra Fazal as Leslie Willis / Livewire, a thief with electrokinetic powers.
Azuri Hardy-Jones as "Flip" Johnson, a young intern at the Daily Planet and friend of Clark, Lois, and Jimmy.
Jason Marnocha as Jor-El, Clark's biological Kryptonian father.
Ethan Avery / Damage, a Task Force X agent who utilizes cybernetic Kryptonian arms that allow him to grow in size.
Reid Scott as Jonathan Kent, Clark's adoptive father.
Kari Wahlgren as Martha Kent, Clark's adoptive mother.
Chris Parnell as Slade Wilson / Deathstroke, an assassin and agent of Task Force X who later becomes Luthor's bodyguard.
Lucas Grabeel as Kyle / Mist, a member of Intergang who uses Kryptonian technology to become invisible and intangible.
Catherine Taber as Siobhan McDougal / Silver Banshee, a member of Intergang and sister of fellow member Mist who wears a Kryptonian mask that grants her a sonic scream.
Vincent Tong as Steve Lombard, a sports columnist at the Daily Planet.
Rough House, a member of Intergang with Kryptonian gauntlets that grant him super strength.
Vulture, a minion of Doctor Poison.
Melanie Minichino as Cat Grant, a gossip columnist at the Daily Planet.
Silver St. Cloud, a philanthropist millionaire.
Whip, a Russian thief with Kryptonite-powered whips.
Marina Maru / Doctor Poison, the princess of Markovia.
Jake Green as Dr. Anthony Ivo / Parasite, the CEO of AmazoTech and creator of the Parasite armor.
Max Mittelman as Lex Luthor, Superman's nemesis. He initially appears as Anthony Ivo's personal assistant before siding with Task Force X and establishing LexCorp as its CEO.
Hank Henshaw / Cyborg Superman, an astronaut who became a cybernetic human following the fight with Brainiac.
Joseph Martin / Atomic Skull, a Task Force X agent who uses a Kryptonian suit that allows him to manipulate radiation.
Thomas Weston, the CEO of AmerTek and the former boss of John Henry Irons and Silas Stone.
Laila Berzins as Rory / Heat Wave, a gang leader who wields Kryptonian flamethrowers. After being captured by Task Force X, Heat Wave is ordered to help capture Superman alongside other criminals. She would later develop a lesbian relationship with Livewire in the second season.
Joel de la Fuente as General Sam Lane, Lois's father and a U.S. Army general.
Debra Wilson as Amanda Waller, a colleague of General Lane and head of Task Force X.
Jessie Inocalla as the Brain, a scientist who originally worked for Project Cadmus and was left as a disembodied brain following an attack by Task Force X.
André Sogliuzzo as Monsieur Mallah, an intelligent gorilla and romantic partner of Brain.
David Errigo Jr. as Mister Mxyzptlk, a trickster from the fifth dimension.
Andromeda Dunker as Vicki Vale, a journalist in Gotham City and a rival to Lois.
Fox, a minion of Doctor Poison.
Michael Emerson as Brainiac, a super-intelligent android and Supergirl's adoptive father.
The Head Steward, one of the robots at the Fortress of Solitude.
Byron Marc Newsome as Dr. John Irons / Steel, a former scientist at AmerTek who was fired by Weston for speaking out against his fusion reactor.
Silas Stone, Irons's colleague who was also fired by Weston for speaking out against his fusion reactor.
Michael Yurchak as Winslow Schott / Toyman, a pawn shop owner, toy maker, robotics and demolitions expert, and an old contact of Sam.
Rhea Seehorn as Lara, Clark's biological Kryptonian mother.
Auli'i Cravalho as Jessica Cruz, a girl who attends Super-Fest and talks positively about Supergirl.
Darren Criss as Jonathan Lane / Jon Kent / Superboy, Lois and Clark's son from a future timeline.
Vella Lovell as Doris Zuel / Giganta, a size-shifting villain.
Chandler Lovelle as Zazzala, the co-head of the dating center W.O.R.M.S.
Erin Anderson as Ms. Gsptlsnz, Mr. Mxyzptlk's wife.
Jolie Hoang-Rappaport as Lara Lane / Supergirl, Lois and Clark's daughter from a possible future timeline.
Steve Blum as Eradicator, a Kryptonian clone created by Luthor using his grey matter sample and Superman's tissue sample. As a prototype for the later Eradicators in a possible future, he can adapt and evolve while also gaining the ability to make brutish duplicates.
