Doc Ock’s death likely plays into his de-aging. In Spider-Man 2, Ock is carrying out a nuclear experiment that threatens to destroy New York City when Spider-Man confronts him. Though artificial intelligence in his metal tentacles corrupted Ock, he’s able to take enough control to destroy his experiment, dying along with it. Since Ock clearly wouldn’t age anymore after dying, Marvel likely needs to de-age him to resemble his look before his death. Because Maguire’s Parker didn’t die in the original Spider-Man trilogy, he wouldn’t need to be de-aged. For him, time should pass regularly.
In an addition to being the most highly anticipated film since Avengers: Endgame, No Way Home has reinvigorated interest in Sam Raimi’s Spider-Man trilogy and Marc Webb’s The Amazing Spider-Man films. Rumors have circulated for months that Maguire and Andrew Garfield’s versions of the hero will appear in the Phase 4 film to help Holland defeat their respective villains. At this point, the enthusiasm and nostalgia felt by the fandom are palpable. Raimi’s trilogy in particular set a precedent responsible for influencing the current state of superhero cinema. Even if Spider-Man 3 fell a little short of the mark set by its predecessor, which is clear in the most iconic scene in the film.
Of course, there could be more Marvel shenanigans at play. If Maguire does appear de-aged, it could be because Marvel is plucking Spider-Man from a specific period in time. In Spider-Man 2, Doc Ock seems to redeem himself in the end. But in the No Way Home trailer, his “Hello, Peter” hints that he’s still a menacing villain. Because of this, it seems Marvel took this version of Doc Ock from a point where he was never redeemed. In all likelihood, Maguire’s Spider-Man will look similar to the actor’s current appearance. However, if Spider-Man: No Way Home also takes Parker from an earlier point in Spider-Man 2, a de-aged Tobey Maguire could swing onto the scene.