Calliope - Calliope is the protagonist of Mankinds Toughest. She is a young girl whom shared a body with her brother but soon got "her own body". She is the creator of the Green Sun.
Bruce Wayne - Batman (real name Bruce Wayne) is the deutratagonist of Mankinds Toughest. He is a crime solving superhero that dresses as a bat and has a grappling hook.
Clark Kent - Superman (real name Clark Kent) is the tritagonist of Mankinds Toughest. He is a man with superhuman strength that gathers supreme power from the Green Sun
Lord English - Lord English is a time traveling demon and the main antagonist of Mankinds Toughest. He shares a body with Calliope. He is the creator of the Red Sun.
The Joker - Joker is the secondary antagonist of Mankinds Toughest. He is a psychotic jester clown that works for Lord English out of fear.
Darkseid - Darkseid is the tertiary antagonist of Mankinds Toughest. He is a powerful supervillain created by the Red Sun.
- Harley Quinn
- John Egbert
- Mobster Kingpin
- Andrew Hussie
- Doc Scratch
- Peregrine Mendicant
- Jack Noir