The two Bird Keeper trainers that you face on Route 20 are named Bert and Ernie, referencing the Muppet duo from the children's television series "Sesame Street" who have a fondness for pigeons and rubber ducks respectively.

The release of Pokémon HeartGold and SoulSilver Version got delayed for Flanders (the Dutch-speaking area of Belgium) and the Netherlands. The reason was because of a save data bug found in English copies of Pokémon HeartGold meant for those two regions. The bug caused certain Pokémon HeartGold copies to not be able to read its save data, even when there was none - rendering the game unplayable.

The game released eventually on April 2nd, 2010 - one week later than the pan European release date (March 26th, 2010).

During the Sinjoh Ruins event, in which Arceus creates a Lv. 1 Dialga, Palkia, or Giratina, a magic circle appears beneath it during the corresponding cutscene, remaining in place for most of the sequence. The layout of this circle is identical to a chart that Game Freak co-founder and prominent series staffer Junichi Masuda created during the development of Pokémon Diamond and Pearl in 2005, detailing the lineage of numerous Legendary Pokémon from the first four generations. This chart did not become publicly available until it was included in the Teraleak, a large-scale leak of internal server data from Game Freak in 2024.

Although the Spiky-eared Pichu obtainable in the Ilex Forest event has a shiny form, this form cannot be obtained in the game itself without hacking.

If playing on a counterfeit cartridge, attempting to play Voltorb Flip in either the Goldenrod Game Corner or Celadon Game Corner will crash the game. It's unclear if this is an Anti-Piracy measure, or if it's a mistake in the ROM of Heart Gold and Soul Silver.

Towards the end of the opening sequence, it displays the 3 Johto starters moving across the screen. Chikorita and Totodile use their in-game sprites. However, Cyndaquil uses a different sprite than what is actually in the game, and this sprite isn't used as Cyndaquil's sprite in any previous or future game, suggesting it may be a beta sprite.

In Cianwood City, if you have only one Pokemon in your team and it does not know Fly or Surf, a generous Trainer in the island's Pokemon Center will give you a Level 15 Tentacool, claiming to have caught too many and was just about to release it before he noticed your situation. This was added to prevent the player from softlocking the game in Cianwood City by giving the player a Pokemon that can learn the Surf HM in order to leave. Additionally, it is possible for the Tentacool given to you to be Shiny.

In Generation II, Cerulean and Fuchsia City didn't use their music from Generation I, and shared themes with Celadon City and Viridian City, respectively. However, when remade, Cerulean and Fuchsia were given their Generation I theme again, but because they didn't have this theme in Generation II, when using the GB Sounds, an original Generation II-styled remix was used.

HeartGold and SoulSilver include the Champions from each of the previous paired versions: Blue from Red and Green, Lance from Gold and Silver, Steven Stone from Ruby and Sapphire, and Cynthia from Diamond and Pearl.

If you interact with your Snorlax in Mt. Silver in the game, it will say; "SNORLAX is feeling very eager". This is due to Red in Mt. Silver also owning a Snorlax. Unique messages will also appear if you interact with Pikachu or Charizard.

The Kimono Girls' dance to summon a member of the tower duo primarily consists of circular motions. In HeartGold, they move clockwise, and in SoulSilver, they move counter-clockwise.

The Togepi that hatches from the egg given to the player by Professor Elm has the egg move Extrasensory. This means that the Togepi's father was either a Hoothoot or a Noctowl.

When you team up with Lance in the Rocket HQ. He has a LVL.40 Dragonite which is 15 levels lower that what it should be. Also, when you fight him for the first time as champion, his three Dragonites are a few levels lower. This also happened in the Game Boy versions.

These 2 games mark the first time that the English versions were announced before the games were released in Japan.

If the game detects that it is being played on a flash cart or emulator, it will freeze at the beginning of a battle with the player's Pokeballs spinning constantly.

There's an item named 'GB sounds' which stands for Game Boy sounds, and is only obtainable after you beat all 16 gym leaders. Despite the fact that the GB Sounds is supposed to sound like the original music from the Game Boy and Game Boy Color, none of the songs sound exactly like the originals. The reason that GB Sounds doesn't perfectly emulate the original soundtrack is due to the games using a sound font for MIDI playback, rather than generating real 8-bit chiptune sounds.