From Monkey Island wiki
The Secret of Monkey Island is a fabled and obscured matter and (with the possible exception of the fourth game) never disclosed to the players of the Monkey Island games. There are numerous proposed secrets. Several characters have gone after the secret, including LeChuck and Herman Toothrot, though their quests have since been retconned.
The original title
The title of the first game, The Secret of Monkey Island, is the first public mentioning of the proposed secret and the search of which is given as the reason for LeChuck's demise. Despite the title, nothing in the game actually seems to indicate what the secret is. Since the game makes a great deal over the use of the Giant Monkey Head, it could be considered the Secret, or else what exists beneath it: the hideout of LeChuck's ghost ship.
However, this would be unlikely as Ron Gilbert, in his own words, has never told anyone what the secret (according to him) is.
In Monkey Island 2: LeChuck's Revenge, the treasure of Big Whoop is heavily believed to potentially be the fabled secret, as it is the focus of much of the action in this game and the last two Parts of The Curse of Monkey Island. However, at the beginning of Part V of the latter, the player can ask LeChuck what the secret is, LeChuck makes a vain attempt to seem mysterious which causes Guybrush to deduce that even the demon pirate doesn't know.
Giant Monkey Robot
The fourth game, Escape from Monkey Island, is heavily indicative that the Giant Monkey Robot is the secret of the Monkey Island, as per the cinematic that introduces it: The real Secret of Monkey Island. This should not taken as a credible plot point, however, as the characters later establish in subsequent games that the Secret is still unknown, with the development staff confirming that the Secret still lies with Ron Gilbert.
- In Escape, when Herman fully regains his memory, Guybrush can ask him what the secret of Monkey Island is. There will then be a list of possible options for what you think it is, including 'The mystery of your [Herman's] missing pants.'
- In The Guinness Book of World Records: Gamers Edition, several questions are asked to Ron Gilbert. When asked what the Secret of Monkey Island is, Ron replies 'Pi.'
- Ron Gilbert has stated that if he ever wins the lottery, he'll buy the rights to Monkey Island and create his own game to follow Monkey Island 2, jokingly called Monkey Island 3a: The Secret Revealed or your Money Back.
- In the PS3 version of Tales of Monkey Island Chapter 2: "The Siege of Spinner Cay", if Guybrush can ask the MerLeader what the Secret of Monkey Island is (to which s/he responds by whispering about the Secret of Donkey Island in his ear), the player is awarded the "Nice Try" bronze trophy in the "PlayStation Network Trophy Achievements".
- Also, in "Launch of the Screaming Narwhal", Guybrush can talk to LeChuck and ask him if he's "trying to learn the Secret of Monkey Island again" by hypnotizing the thirteen Monkeys of Montevideo, to which LeChuck answers no. In the PS3 version, this is one of the references to find in the right order prior to meeting the Voodoo Lady and examining Nor Treblig's shrine in order to earn the player a "Why Is My Older Brother Laughing?" bronze trophy.
- In "Lair of the Leviathan", while Guybrush is still in the Voodoo Lady's body and speaking with the Marquis De Singe, Guybrush can ask him, "Do you have any secrets you'd like to share? Perhaps concerning Monkey Island?", at which point De Singe calls the island "zat worthless rock on top of all zat lava" and says nothing on the Secret, but adds, "I hear ze wildlife is quite cheeky."