The Akatsuki could also be antagonists in naruto x female sasuke fanfiction. They might target female Sasuke because they see her as a threat or as someone who could be useful to their plans. Naruto and female Sasuke then have to fight against the Akatsuki's various members to protect themselves and the village.
In some fanfictions, a new character could be created as the main antagonist. This character might be jealous of Naruto and female Sasuke's growing relationship and power. They try to create rifts between them and stop them from achieving their goals.
There could be an outside force, like a neighboring village that wants to keep Naruto and Sasuke away from their own village. They might be afraid of the potential power and influence Naruto and Sasuke could bring back if they return. So, this neighboring village sends their best ninjas to hunt down Naruto and Sasuke during their banishment, making them the main antagonists in the fanfiction.
In this kind of fanfiction, the Fallen Angels could be main antagonists. They might see Naruto and Sasuke as threats to their plans in the DxD world.
It could be an original character created just for the fanfiction. Maybe a powerful ninja from a forgotten clan who has a vendetta against Konoha and targets Naruto, Sasuke and Sakura specifically.
Orochimaru could be a likely antagonist. In the original Naruto story, he had a strong influence on Sasuke. In the fanfiction with Fem Sasuke, he might manipulate her to turn away from Naruto, causing Naruto's heartbreak. Another could be Danzo. His underhanded and power - hungry ways might lead him to interfere in the relationship between Naruto and Fem Sasuke, perhaps by setting up situations that make Fem Sasuke distrust Naruto.
Well, it could be Orochimaru. Even if they travel in time, Orochimaru's thirst for power and knowledge might make him an antagonist. He could see Sasuke and Shikamaru as threats to his plans, especially if they are trying to change the past which might interfere with his own schemes.
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.
Maybe a powerful vampire from Moka's world who sees Naruto as an intruder and wants to get rid of him. This vampire might also be jealous of the bond between Moka and Naruto and tries to break them apart by creating chaos and fighting against them.
There might be some ancient forces or entities that are awakened by Naruto and Sasuke's new 'godlike' status. These could be demons or spirits that were sealed long ago and now see Naruto and Sasuke as threats to their plans of domination. They would be very powerful and require Naruto and Sasuke to use all of their enhanced abilities to defeat.
Some of Naruto's former friends who have been influenced by the negative propaganda against him could also be antagonists. They might be misled into believing that Naruto has changed for the worse. They could actively oppose Naruto, either by trying to capture him or by preventing him from doing certain things. Another possibility is that there could be a hidden group within the village that has a vendetta against Sasuke and, by extension, Naruto for bringing him back.
In a few fanfictions, it could be a jealous ninja within the village. Maybe someone who has feelings for Naruto and sees Sakura as an obstacle. This ninja could create a false narrative that leads to Sakura's banishment, thus becoming the main antagonist in the story.