Emu Hojo. A pediatric intern with genius-level gaming skills. Usually quiet and gentle, he shows a confident and hot-blooded side when it comes to games. His creed is to give his all to both "saving the patient's life" and "clearing the game." He carries the Bugster Virus within him, which is the source of his ability to transform into Ex-Aid. He is a hero who protects people while carrying the dual missions of a doctor and a Kamen Rider.

Hiiro Kagami. A calm and collected genius surgeon at CR. He always prioritizes rationality and has a stoic personality that hates waste, but he hides strong convictions and kindness within. Having lost his lover to the Bugster Virus in the past, he is obsessed with saving patients to overcome that sorrow. He fights with a swordsman-like combat style and is a highly skilled Rider who reliably takes down enemies.

Poppy Pipopapo is a Bugster and a bright, energetic mood maker. While supporting the Riders as a navigator, she is a key character who develops a human-like heart through the battles.

Taiga Hanaya. The user of Kamen Rider Snipe and a dark doctor who once had his medical license revoked. He has a blunt and rough personality but holds a strong conviction to save patients. Carrying the past of losing comrades in an incident five years ago, he continues to fight Bugsters as atonement. He is a skilled fighter who uses a gun-based combat style, wielding pinpoint accuracy as his weapon.

Kiriya Kujo. A medical examiner and the user of Kamen Rider Lazer who pursues the truth behind the Bugster incidents. He has a breezy, lighthearted personality that messes with those around him, but possesses sharp insight and a strong sense of justice. He is a reliable ally who acts without fear of danger for the sake of the truth.

A self-proclaimed God. "I am God!!" A meme-worthy character and the user of Kamen Rider Genm. He is the CEO of Genm Corp and a genius game creator. A man who possesses intense self-confidence and madness to the point of calling himself "God," he is the very person who created the Bugster Virus. While showing a ruthlessness that treats even human lives as part of a game, he developed numerous Gashats with overwhelming creativity and obsession. He is a key person who drives the story forward, a unique Rider combining madness and charisma.

A Bugster who also fights as Kamen Rider Para-DX. He loves games above all else and has a bellicose personality that enjoys fighting strong enemies, but human-like emotions begin to sprout through his relationship with Emu. He is a key character who undergoes significant growth throughout the story.

Masamune Dan is the user of Kamen Rider Cronus and a ruthlessly cold businessman. He manipulates time-stop abilities to corner the Riders with overwhelming power. He is a heartless ruler who chooses any means necessary to achieve his goals. In this work, he serves as the final boss type.