It could be an envious noble. This noble might be jealous of Sakura's position as a princess and her popularity among the people. So, they try to spread false rumors about her and plot to dethrone her.
A rival princess from another kingdom could be the main antagonist. This rival princess might feel that Sakura is unworthy of her position and wants to claim the throne for herself. She would use her own charm, political connections, and perhaps some underhanded tactics to try and remove Sakura from power.
In the fanfiction, the main antagonist could be a dark and ancient force that has awakened. Sakura fakes her death to get closer to this force without it suspecting her. She then tries to find a way to defeat it, while the force believes it has eliminated one of its potential threats.
Maybe it's a rival within the mafia. Someone who sees Sakura as a threat to their own position or power. This person could constantly try to undermine her and make her life in the mafia even more difficult, even if the mafia boss doesn't have any ill intentions towards her at first.
Another possible antagonist could be a jealous relative. For example, a cousin who believes they should be the heir instead of Sakura. This relative could spread false rumors about her, or try to sabotage her efforts to prove her royalty in more subtle ways, like stealing important documents or artifacts related to her claim to the throne.
Well, perhaps in the fanfiction, Sakura Haruno is suddenly transported to a magical realm where she is a princess. She meets all sorts of strange and wonderful creatures. She uses her medical ninjutsu skills to help the sick in the kingdom and gains the love and respect of the people. But there is a dark wizard who wants to steal her power, and she has to fight against him with the help of her new friends in this realm.
In this fanfiction, the main antagonist could be a strict teacher. Sakura, being a boy with a free - spirited nature, often clashes with the teacher's rigid rules. The teacher always seems to be out to get Sakura, giving him unfair punishments and trying to suppress his creativity or individuality.
It could be some of her jealous peers. For example, those who are envious of Sakura's skills or her closeness to certain important characters in the Naruto universe. They might spread malicious gossip about her to make her an outcast.
Sakura might meet the founders of the village. For example, she could meet Hashirama Senju. He was a powerful and visionary leader. Meeting him could give Sakura insights into the true origins of the village and how to better protect it. She could also learn some of the ancient ninja techniques from him.
One possible antagonist could be a popular girl in school who is jealous of Sakura's popularity and tries to undermine her at every turn. For example, she might spread false rumors about Sakura or try to steal her friends. Another could be a strict teacher who doesn't believe in Sakura's abilities and is always giving her a hard time, like constantly doubting her work in class or not allowing her to participate in certain school activities.
It could be a powerful dark wizard who wants to use Sakura's powers for his own evil purposes. He might be constantly trying to capture her or manipulate her into doing his bidding.
Another potential antagonist could be an enemy that Orochimaru and Sakura face together during her training. This enemy might have a vendetta against Orochimaru and see Sakura as an extension of him. So while Orochimaru is training Sakura, this new enemy could be the one causing the most immediate problems and danger for them both.