The Minecart Skip Glitch can be triggered if the player performs a jump within perfect timing during the Minecart level in Chapter 4-3, allowing the player to move Leon through the whole level, skipping the entire section where Ganados would normally jump from above. The level can be sped through much faster if the Ditman Glitch is actived.

The reload animation for the Handcannon is different before and after it is fully upgraded. Before the weapon is fully upgraded, Leon will reload the Handcannon with four bullets. However, once it is fully upgraded, the reload animation will change to Leon reloading the Handcannon with a speed loader.

When playing as either Krauser or HUNK in The Mercenaries game mode, their respective theme music is the Fourth and Eighth Mission Tunes from the game P.N.03, which was also developed by Capcom.

On a bulletin board in the room with security monitors that's shut off when Leon sees Ashley, there's an image of a hamster-like monster. This is actually taken from the cover art of Bloodwych, a 1989 RPG dungeon crawler, originally developed for the Commodore 64 and eventually released on half a dozen 8-bit home computer systems.

In the Japanese release of the game, the sections in Chapter 3-4 where you play as Ashley feature fixed, dynamic camera angles akin to Resident Evil Code: Veronica that are not found in the international releases of the game.

After the helicopter scene with Mike you can see a person hiding behind a pillar in the distance past the ruins and rubble when using the sniper rifle with an extra scope. It is unknown who this person is, though it is likely it is someone from the development team or someone related to them.

Though largely unused in-game, the characters Hunnigan and Mike have complete character models that can only be seen through camera hacks.

Hunnigan appears in-game during her radio conversations with Leon, where only her head and shoulders are visible. However, moving the camera reveals that these conversation are simply full character models of Leon and Hunnigan sitting next to each other behind a radio texture. Additionally, Hunnigan's model contains multiple layers of clothing, including a layer for both her blazer and blouse. Digging through the game's files also reveals a texture for a white blouse with a black bra and skin clearly visible underneath it.

Likewise, Leon's pilot Mike is never seen outside of his helicopter in-game. Moving the camera into the helicopter during his scenes, however, reveals a full character model inside of the cockpit. Oddly, the character model has yellow eyes, a trait usually associated with the game's monsters.

The lurching man is an unused creature designed for Resident Evil 4, which was planned to be able to change forms. Unfortunately it never got past the design phase.

The "Electric Man" was a creature designed for Resident Evil 4, although it didn't make it past the design phase.

The "Living Doll" is an unused enemy from the second prototype, (also known as the "Hallucination" build), it appeared in the E3 2003 demo for Resident Evil 4. Which at the time featured Leon being attacked by hallucinations.

Concept art exists for an unused "Parasite Woman" enemy, in both an "A-Type" and "B-Type". The "A-type" shows her bound in a straitjacket, and one of her arms has grown to gargantuan lengths. It would appear that her design was reused for the J'avo in Resident Evil 6.
The "B-Type" variant has no arms free at all, and her head has transformed into a sharp-toothed monster.
The third piece of concept art is an unbound woman in a tattered dress, armed with a shotgun.
The final design, merges the earlier designs - an unbounded woman with two inhuman arms growing next to normal ones, while a monster's face projects from the side of her head.
The creature's straight-jacket concept shares an uncanny resemblance to the Nosferatu From Resident Evil Code: Veronica X and Lisa Trevor from the Resident Evil remake.

Any instances of decapitation were strictly removed from the Japanese release.

During the segment of the game when playing as Ashley, it is possible to open a door into a Zealot to stun them and then perform Leon's suplex move on them. This glitch is only present in the GameCube version of the game, and was edited out in all other versions.

Nuby Tech, a gaming peripheral company, created a chainsaw-shaped controller inspired by the Chainsaw Man enemy in Resident Evil 4. Separate versions were made for the GameCube and PS2. However, it didn't enhance the playing experience, and was criticized for its poor button layout.

The gun Broken Butterfly has a description which references the film Sudden Impact. In the movie, a character says "Go ahead, make my day" while holding a revolver. The description for the Broken Butterfly reads: "This will make anyone's day."

The title menu for Ada's Separate Ways Campaign was likely inspired by the movie poster for La Femme Nikita.

When the player attempts to look up Ashley's skirt she will exclaim "UGH! You PERVERT!" Or "HEY! What are you looking at!" and cover herself. Humourously, this will trigger if Leon's head ends up directly under her skirt in any situation including if he is knocked down by enemies.

If Ashley is wearing any of her alternate costumes, this animation will not trigger.

During the standoff with the Ganados in the cabin, shooting Luis enough times will trigger a cutscene where he will shoot and kill Leon, resulting in a game over.

Trying to reload the Chicago Typewriter (which has infinite ammo by default) while wearing the Leon's Mobster Outfit instead triggers a small taunt wherein he adjusts his hat and scoffs. If the player reloads 4 times in a row, a more dynamic animation will play of Leon tossing and catching his hat.

The gun Killer7 is a reference to a game by the same name, produced by Shinji Mikami and published by Capcom. A character in Killer7 used a similar looking gun.