It could be Kaguya. If Kaguya were to return and use her powerful abilities to drive Naruto mad, perhaps by invading his mind with dark thoughts and memories. She has the power to warp reality and minds, so she could easily make Naruto lose his sanity. And since she has a grudge against the world of ninjas, making Naruto, one of the most powerful ninjas, go insane would be a great way for her to start her reign of terror all over again.
Danzo could be the main antagonist. He was always a shady character in the Naruto series. In a fanfiction, he could frame Naruto for heinous crimes against the village. This false accusation could lead to Naruto being ostracized and hunted. The constant stress and betrayal would cause Naruto to lose his sanity. And Danzo, with his own political motives and thirst for power, would do everything he could to keep Naruto in a state of chaos.
Perhaps an unknown and powerful dark ninja. This ninja could be from a long - forgotten clan with dark powers. They might have a vendetta against the Leaf Village and see Naruto as the key to their revenge. So they use their dark arts to make Naruto lose his sanity and turn him against his own village.
Maybe Orochimaru manages to get his hands on Naruto and subjects him to some dark and twisted experiments. These experiments could mess with Naruto's mind, causing him to lose his sanity. He could start seeing illusions all the time, believing his friends are his enemies. As a result, he'd be in a constant state of confusion and aggression, and his once - positive attitude towards life and ninja - hood would be completely gone.
It could be Orochimaru. He's always been interested in Naruto's power. Maybe he devises a plan to make Naruto lose his memory so he can manipulate him more easily, perhaps to use him as a weapon against the Hidden Leaf.
A new and mysterious dark ninja could be the main antagonist. This character might have a special ability to corrupt others. They target Naruto specifically because of his power and influence. By using some form of dark jutsu or psychological manipulation, they make Naruto lose his humanity, turning him into a weapon against the very people he used to protect.
The Akatsuki could be the main antagonists. They might think that Naruto's voice holds some key to a powerful weapon or secret. So they send one of their members, like Zetsu, to steal Naruto's voice. Zetsu's ability to blend in would make it easier for him to get close to Naruto and carry out the deed.
It could be a new, powerful ninja from a hidden village. This ninja has a special ability to manipulate the chakra related to emotions. He sees Naruto as a threat because of his popularity and power, so he uses his ability to make Naruto lose his emotions, hoping to weaken him and his influence.
It could be a rogue ninja from a hidden village that has a grudge against Naruto. This ninja might have a special jutsu that specifically targets Naruto's left eye during a fight, causing him to lose it.
Obviously, Harry Potter himself is the central character. Since the story is about him losing his sanity, he is at the core of the plot. Then there would likely be his friends like Hermione and Ron. Their reactions to Harry's deteriorating mental state would be important aspects of the story. They might try to help him, or they could be at a loss about what to do.
It could be a new and powerful rogue ninja who manages to overpower Naruto and cause him to lose his arm. Maybe this antagonist has some sort of vendetta against Naruto or the Hidden Leaf village.
It could be that Naruto discovers some dark secrets about his past, like his parents were actually killed by the very people he trusted in the village. This revelation is so shocking that it shatters his mental state. He becomes a completely different person, losing his sense of right and wrong, and his sanity along with it.