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.
One possible plot could be that Naruto experiences repeated and extreme betrayals. For example, if his friends in Konoha turn on him due to false accusations of him being a threat. This would gradually chip away at his mental state, making him question his values and identity, and slowly drive him insane as he feels isolated and persecuted.
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 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.
The Caterpillar could be the main antagonist. He has always been a bit of an enigma in Wonderland. Maybe as Alice shrinks, he sees her as a threat to his control over the small part of Wonderland he rules and tries to stop her from exploring further.
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.
The Organization in the Claymore world could be the main antagonist. They already have a lot of secrets and do some morally ambiguous things. If Naruto shows up and starts changing the status quo, like teaching Claymore warriors to be more independent, the Organization might see him as a threat and try to eliminate him.
It could be a rogue ninja who was once a student of Orochimaru and has now developed his own dangerous jutsu. He wants to take over the ninja world and believes the old ways are holding everyone back.
Orochimaru could be a great antagonist. He might want to use Shenron's power for his own dark experiments. He could try to steal the dragon balls and manipulate the wishes to gain immortality or create an army of powerful, immortal ninja.
It could be someone who opposes Naruto's newfound admiration for Ganondorf. Maybe a traditionalist ninja who thinks Naruto is straying from the true ninja path by getting influenced by Ganondorf.
Lex Luthor could be a great antagonist. He's always looking for power and knowledge. If he discovers Naruto's abilities, he might try to use them for his own gain or see Naruto as a threat to his plans in Smallville.