| Role | Character | First Appeared in Gen: |
| The leader of Team Aqua who steals the Red Orb and tries to awaken Kyogre | |
| The leader of Team Magma who steals the Blue Orb and tries to awaken Groudon | |
| The former Champion of the Hoenn Elite Four, who left his position to pursue his interest in rare rocks and stones | |
| A family of avid Pokémon trainers who challenges the player to consecutive Pokémon battles | |
| The man who owns the Trick House and challenges the player to retrieve a scroll in maze-like puzzles | |
| The owner of the Hoenn Battle Frontier who seeks out talented Pokémon trainers | |
| The programmer who runs the Pokémon Net Center on Knot Island, and grants the player the Rainbow Pass | |
| A computer technician who upgraded the Pokémon storage system for the Hoenn region | |
| A Pokémon professor from Sandgem Town whose studies specialize in Pokémon evolution | |
| The assistant of the Professor in Sandgem Town who also helps to collect data for the PokéDex | |
| The Champion of the Sinnoh Elite Four who gives you the SecretPotion and accompanies you into the Distortion World where Giratina resides | |
| A Pokémon trainer who asks for you to accompany her through Eterna Forest | |
| A Pokémon trainer encountered on Iron Island who has a partner Lucario | |
| A Pokémon trainer the player finds lost in Wayward Cave and helps guide back to the entrance | |
| A Pokémon trainer who accompanies you in Stark Mountain and takes the Magma Stone | |
| A Pokémon trainer found in a previously blocked area of Victory Road who has a partner Arcanine | |
| The Team Galactic commander who lead the invasion of the Valley Windworks | |
| The Team Galactic commander first encountered in Team Galactic's Eterna Building | |
| The Team Galactic commander who lead Team Galactic's operation at Lake Valor to capture Azelf | |
| The leader of Team Galactic who views emotions as unnecessary and strives to create his own new world | |
| A Team Galactic commander who eventually takes over as the leader of Team Galactic and tries to capture Heatran | |
| An International Police officer investigating Team Galactic's operations | |
| A computer technician from Hearthome City who designed Sinnoh's Pokémon storage system | |
| The owner of Amity Square and Pokémon Mansion who likes to brag about the rare Pokémon in his Trophy Garden | |
| The leader of the Battle Tower and the father of the player's rival in DPPt | |
| The character who owns a Marill and whose grandparents run the Day Care Center in Johto. | |
| He liked the Kanto region's Safari Zone so much that he opened up another in the Johto region. | |
| The silent Pokémon trainer who is found training atop Mt. Silver | |
| The grandson of Prof. Oak and rival of Red who becomes the Viridian Gym leader | |
| The player-controlled protagonist from New Bark Town. | |
| The antagonistic rival with a strong dislike of Team Rocket who steals a Johto starter Pokémon | |
| The impulsive and impatient Sinnoh rival who is always in a hurry | |
| The remaining leaders of Team Rocket after Giovanni disappeared. They were given official names in Gen IV. | |
| It is usually found around Cinnabar Island or Seafoam Islands and enjoys corrupting game file data | |