MediEvil 2 contains several of the original forms of gameplay that were present in the first game. Whilst featuring many of the classic swords and other medieval weaponry, long range weapons are more modern, taking the form of pistols, shotguns and a Gatling gun. Progress through the game is a bit more linear and story driven.
- Sir Daniel Fortesque - The protagonist of the game. An ancient hero reawakened to fight a powerhungry necromancer, much like he was 500 years ago. Compared to the first game, his design was slightly modified. His head is a little larger, and he also wears leather gloves.
- Professor Hamilton Kift - A nervous, fast-talking professor in the laboratory near an unused underground rail station. He's a somewhat short man with mechanical hands and a large head. He is skilled in many forms of science, philosophy, the occult and has a knack for creating inventions.
- Princess Kiya - A soft spoken mummy who has been dead inside her tomb for thousands of years and enunciates every word she says carefully. She knows embalming techniques and is grateful to Sir Dan for having rescued her from her eternal prison.
- Lord Palethorn - The villain of the game. His motive is to find all the lost pages of Zarok's spellbook so he can gain control of London and eventually, the world.
- Mander - Lord Palethorn's associate, he was turned into a lizard during the dark spell. He follows Palethorn out of fear.
- Dogman - Dogman is Lord Palethorn's muscle man. He was also another victim of Palethorn's spell, turning him into a dog. He follows Palethorn out of stupidity.
In Kensington in the year 1886, 500 years after Sir Daniel Fortesque's climactic battle against the evil sorcerer Zarok, a sorcerer named Lord Palethorn discovers Zarok's spell book and casts the Spell of Eternal Darkness over the city of London. However, the pages of the book soon scatter across London. The spell also once again resurrects Sir Dan, who was resting at a nearby museum. He is recruited by a professor named Hamilton Kift and his ghostly sidekick Winston to recover the pages of Zarok's spellbook and put a stop to Palethorn's plans. Along the way, they end up being joined by a mummy princess named Kiya, who becomes Dan's love interest.
During an incident in which Kiya goes off on her own, she is killed by Jack the Ripper, much to the shock of Dan. Discovering a time machine, Dan travels back in time in order to save Kiya, merging with his past self to gain super armour. As Dan finally confronts Palethorn, he steals the pages from him and uses it to summon a demon. However, Dan manages to turn the demon against Palethorn, putting a stop to both of them.