All of the surviving voice actors from the Duck Tales TV series reprised their roles for the game, including Alan Young, who was 93 at the time of recording.

Hal Smith (Flintheart Glomgold, Gyro Gearloose) passed away in 1994, while Hamilton Bob Camp (Fenton Crackshell/GizmoDuck) passed away in 2005, and Joan Gerber (Mrs. Beakley) in 2011. Thus other actors had to be found to voice their characters.

The title screen of the game mimics a part of the original cartoon intro.

There is an Easter egg referencing the original game, where a statue in the Amazon level falsely suggested that you pay $300,000 to advance. Breaking the statue in the remake will unlock the achievement "Score to Settle."

The original African Mines level on the NES required you to unlock a gate by getting a key in Transylvania. In Remastered, the path is clear and you don't have to find a key, but in the background you can see the same lock from the first game where the gate was originally located.

The credits music (A piano version of the theme from the Moon level) was originally planned to only be played at Comic-Con. The developers decided to put it in the final game, likely after the positive feedback it received.

A sprite of Scrooge in the costume he wore in the "Masked Mallard" episode of the Ducktales cartoon series appears in a documentary about the making of the game. This could possibly indicate that the developers originally planned to give the player the option to change Scrooge's outfit.

Within the game's files are a number of unused images referring to Shantae, another character created by WayForward. It's possible that Shantae would have appeared as a playable character at one point during development, but was later cut. This is speculation, but it is evident that Shantae was at least used as a placeholder during development.

The developers went though the entire cartoon series and picked episodes that matched the original levels of the DuckTales game to draw inspiration from for the background art.

During development of DuckTales Remastered, WayForward went through six different designs for Scrooge when developing the game (using the NES sprite from the original game as well as how Scrooge appeared in the original DuckTales cartoon for reference). The designs, in order, are based on the following:
1. The NES sprite design (having Scrooge in both red and blue outfits)
2. A updated version of the NES design sprite
3. A design based on his appearance in DuckTales but with different colored cuffs and a black top hat
4. A design based on how Scrooge appeared in the Carl Barks comics (with a black top hat)
5. A reworked design of the Carl Barks Scrooge (with a bit of red showing in the top hat)
6. A design based on how he appeared in the Don Rosa stories of Scrooge

The game's data contains a different tune of the Himalayas theme, which starts off with a high pitched string instrument, rather then the style used in the final version of the game.

Upon completing the game on Extreme Difficulty, the text that would normally say "Thanks for Playing" is replaced with one that says "Dream and Friends", referencing what was said by Scrooge to his nephews in the ending of the prototype version of the original NES game.