The main antagonist could be Naruto himself in a sense. Since he has gone insane, his actions are now unpredictable and harmful to the people around him. His former friends, like Sakura or Kakashi, might have to step up and try to stop him, seeing him as the new threat.
It could be a new dark wizard who has the power to manipulate minds. This wizard might target Harry specifically, driving him insane as part of a larger plan to take over the wizarding world. Since Harry is seen as a hero, if he goes insane, it would create chaos and make it easier for the antagonist to achieve his goals.
It could be Sasuke. If Sasuke decides to fully embrace the dark side and wants to bring chaos, he might target Naruto specifically. His actions and taunts could be what drives Naruto insane.
Maybe it could be a new character who is a combination of ninja and wizardry evils. This character could be jealous of Naruto's unique abilities that bridge the gap between two different worlds and wants to stop Naruto from uniting the ninja and wizarding communities against him. They could have powers that are a mix of dark magic and some dark ninja jutsus.
The Hidden Leaf Village itself could be the main antagonist. If they turn on Naruto for no good reason, they become the force he has to fight against as a rogue ninja.
It could be Danzo. He's always been a bit of a shady character in the Naruto series. He might see Naruto as a threat to his power and influence in the village. So, he could frame Naruto for some crime and get him sent to jail just to eliminate his competition.
In some cases, it could be a new and powerful enemy. This enemy might have the ability to manipulate chakra in a way that affects Naruto's mind. For example, they could send out waves of negative chakra that slowly erode Naruto's mental state. Over time, these attacks make Naruto go insane as he struggles to fight against this unseen and insidious force.
Another possibility is that there is a rogue ninja in Kumo who uses Naruto's neglected state to his advantage. He might try to manipulate Naruto into doing things that would be bad for both Naruto and Kumo, all while remaining in the shadows and making it seem like Naruto is acting on his own accord.
It could be an unknown force that manipulates the events around Naruto to drive him insane. This force could be an ancient evil that has a vendetta against the Uzumaki clan. It secretly plants seeds of doubt and chaos in Naruto's life, causing him to question everything he knows and trusts, slowly pushing him over the edge.
Another possibility is Madara Uchiha. Even if he is not fully alive in the original story, in this fanfiction, his spirit or some form of his influence could be present. He could manipulate Naruto's new evil state for his own ends, like trying to destroy the ninja world that he once had a vendetta against.
Madara Uchiha could also be a likely cause. If he somehow managed to return or had a long - planned scheme that involved breaking Naruto's sanity. He was a very powerful and devious foe who could use his knowledge of the ninja world and its powers to target Naruto's mental stability.