Perhaps a rogue ninja group that has a vendetta against Anko. When she forms this new family with Naruto, they target the whole family unit to get back at her. They might see Naruto as a way to get to Anko or vice versa, and constantly attack and create chaos for them.
Anko might not be a traditional antagonist, but if she is siding with Evil Naruto for some reason, she could be seen as an antagonist from the perspective of the other villagers. However, it's also possible that she is being manipulated herself, in which case the true antagonists would be those doing the manipulating.
It could be Orochimaru. Even though he was defeated before, he might come back with a new plan. Maybe he wants to use Naruto and Naruko's family for some dark experiment, like trying to extract the unique chakra combination that their family might have.
Maybe a new group of rogue ninjas who see Naruto as a threat to their plans. They've kidnapped him and are holding him captive. Anko would then have to fight these ninjas who are well - trained and have their own unique abilities. They might be after Naruto's Nine - Tails chakra for some evil purpose.
A powerful dark guild could be the main antagonists. They might be jealous of the combined power of Natsu and Mirajane's family and seek to destroy them to gain more power in the magical world.
It could be a rogue ninja from a hidden village who has a vendetta against Konoha. This ninja might target Kurenai and Anko specifically because of their skills and knowledge, and Naruto gets in the way while trying to protect them.
It could be his own family members who abandoned him. They might come back as antagonists, trying to stop Naruto from reaching his full potential or causing trouble for him out of envy or regret. Maybe they have joined a dark force and are now working against him.
It could be Orochimaru. He has always been interested in power and the secrets of the tailed beasts. So, he might see Naruto and the Jinchuuriki family as a source of great power to experiment on or steal from.
One possible antagonist could be a powerful wizard or sorcerer who is jealous of Naruto's growing influence and the harem he has. This antagonist might try to break up the group and steal their powers.
There could be a powerful and jealous ninja from another village. This ninja wants the power of the Shukaku for himself. He sees the relationship between Naruto and the female Shukaku as an obstacle to his goal, so he devises plans to separate them and capture the female Shukaku, making him a major antagonist in the fanfiction.
It could be some hidden members of Naruto's family itself. Maybe there are relatives who have been manipulating things from the shadows and their actions led Naruto to believe he needs to take revenge on the family as a whole.