Another possibility is that there could be a new, original antagonist created specifically for the fanfiction. This character could be someone who has a grudge against Naruto's family and wants to destroy their bond. They might try to turn Naruto against his sister or vice versa, creating internal conflict within the family while also posing an external threat.
The main antagonists could be the traditional Naruto villains like Orochimaru or the Akatsuki members. They might target Naruto's sister as a way to get to Naruto, seeing her as a weakness or a way to manipulate him.
The Akatsuki could be the main antagonists. Since Naruto is an important target for them, and if Kurenai is now his sister, they might see her as an obstacle in their way. They could try to use their various powers and strategies to either capture Naruto or cause harm to both him and Kurenai.
It could be some rogue ninjas who are after Lemon for some reason. Maybe they think she has a special power that they can use for their evil plans.
There could be other rogue ninja groups who see Naruto's sister as a threat or a valuable asset. They might try to either eliminate her or force her to join them. These groups would be antagonists as they oppose her in her new rogue lifestyle and she has to constantly fight or outwit them.
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.
It could be a new group of rogue ninjas who oppose the ideals of the Hidden Leaf Village. They might target Kakashi's daughter because of her connection to Kakashi and Naruto, seeing her as a symbol of the village's new generation of strength.
It could be anyone really. It might be some of the traditional Naruto villains who find a way to cross over into Ruby's world. Or perhaps it could be new villains created specifically for this fanfiction that are a threat to both Naruto and Ruby.
One possible plotline could be that Naruto's sister secretly helps him during his difficult times in the village. Maybe she provides him with extra training resources or helps him outwit the bullies without him knowing it's her at first.
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.