Peace Walker was originally named "Metal Gear Solid 5: Peace Walker". The number "5" was dropped later on, but Kojima personally directed the project, and considered it to be "an MGS5-class game".

In the Main Ops mission, "Infiltrate the Crater Base", series creator Hideo Kojima can be found in the truck with the license plate "63824". Finding him will automatically recruit him to Mother Base.

Originally, Kojima was not going to be a part of the creation of the game aside from providing the overall guidelines and concepts for the project. However, he noticed that the team did not understand the story's themes about nuclear deterrence and the cold war (admitting that it was most likely because of generational differences) and stepped in to make sure the game turned out how he envisioned.

The character "Cécile Cosima Caminades" is based on the French Communications Manager of Konami, "Cécile Caminades".

In the mission, "Dead Man's Treasure", The End from Metal Gear Solid 3: Snake Eater makes a cameo by "contacting" Big Boss from the grave via the Codec (frequency 0.00).

According to director Hideo Kojima, Kaz's design in Peace Walker was partly based on the captain from the film, "Westworld", although the development team had never heard of the film.

On Main Ops 16, the player can get onto the roof of a miner's shack and trigger a special button prompt that, when pressed, has the player jump with their arms spread into a box full fo straw, accompanied by the sound of an eagle's cry. Once the player has completed the Leap of Faith, Kazuhira Miller explains the history of the "Assassin's Straw Box," stating it was used by an order of assassins in the time of the crusades. This is a reference to Assassin's Creed and the Leap of Faith the assassins do. The box is then unlocked for use in future missions. The box even allows the player to knock out guards while hiding in it, similar to how Ezio could assassinate guards from a bundle of straw.

The torture scene in which Dr. Strangelove electrocutes Snake with a lightning rod was altered from the original Japanese version. In the Japanese release, Dr. Strangelove uses a "Laughing Rod" to torture Snake.