Well, the main antagonists could be a group of rogue ninja who are hired by a powerful nation to take down Naruto. Since he is unkillable, they would have to use more underhanded tactics like trying to isolate him from his friends and allies. Or perhaps there is a dark force that is awakened by Naruto's unkillable state, thinking that he is a threat to the balance of the ninja world. This dark force could then become the main antagonist, trying to destroy Naruto at all costs.
Well, in such a fanfiction, Naruto might be unkillable because of some special power-ups. Maybe he has some kind of indestructible chakra shield that constantly protects him from any harm. It could also be due to a unique bond with a powerful entity that grants him immortality. Another possibility is that his willpower is so strong that it literally defies death, allowing him to survive any fatal situation.
Some fanfictions might feature rogue ninja as antagonists. These rogue ninja are after the bounty on Naruto's head or they are trying to steal Jiraiya's knowledge. They attack Naruto and Jiraiya during their travels, making it difficult for them to reach their destination.
Often, it could be the Akatsuki. They are always after the power of the tailed beasts, and with Naruto being protected by the Kyuubi, they would be major antagonists. They might come up with new and devious plans to try and get to the Kyuubi within Naruto.
Maybe a group of dark - type Pokémon that have banded together and are trying to overthrow Arceus. They view Naruto as an easy target at first, but quickly realize he is a formidable opponent with his ninja skills and new Pokémon - related powers. They would constantly try to undermine Naruto and his efforts to protect the Pokémon world.
It could be some rogue ninjas who are against Naruto's new peaceful policies as Hokage. They might see Hinata as a weakness to be exploited to get to Naruto.
The Akatsuki members might also be antagonists. Since they're after the tailed beasts, Naruto with his additional power of lightning control would be a prime target. They might send their most powerful members like Pain or Itachi to deal with him.
It could be a group of rogue ninjas who also ended up on the island. They might be after some valuable resource on the island and see Naruto and Tsunade as obstacles.
The Sound Ninjas could be great antagonists. They could use their own unique parkour - like skills to try and stop Naruto. They might be chasing him through the forest, and Naruto has to use his parkour skills to outmaneuver them.
Often, the Akatsuki still remain as main antagonists. Since Naruto's fusion with the Kyuubi makes him more powerful, they would be even more interested in capturing him for his power.
Maybe an ancient evil that has been awakened. This entity is so powerful that it takes the combined godlike powers of Naruto and Kushina to stand against it. The antagonist could have some connection to the origin of chakra or an old, forgotten curse.