Guardians are enemies that protect the entrances to several biomes. Various bonuses apply to give a damage bonus to guardians. These include amulets and tomes, pets, and shop upgrades.
| Guardian | Universal Damage Needed |
|---|---|
 Wrestler
|
~16,000 |
 Mad Astronaut
|
~160,000 |
 Escaped Alien
|
~1,600,000 |
 Red Invader
|
~16,000,000 |
| Forbidden Area | |
 Dump Guardian
|
~75,000,000 |
 Mutated Experiment
|
~150,000,000 |
 Escaped Crab
|
~3,000,000,000 |
 Guardian of the Room
|
~90,000,000,000 |
| Another World | |
 Guardian of the Alternative Universe
|
~4,500,000,000,000 |
| Gate - Final Three | |
 Lost Wanderer
|
~9,000,000,000,000 |
 Lost Guardian
|
~9,000,000,000,000 |
 Fungi Guardian
|
~1,800,000,000,000,000 |
 Sleeping Guardian
|
~900,000,000,000,000,000 |
| Another World | |
 The Unkillable
|
~3,200,000 |
 Ghost
|
~32,000,000 |
 The Many-Eye
|
~320,000,000 |
 Demon Bear
|
~3,200,000,000 |
 Lunar Dweller
|
~32,000,000,000 |
 The Ancient
|
~320,000,000,000 |
 Predator
|
~3,200,000,000,000 |