Maybe it's an ancient evil that was sealed away long ago and the colossus contract is the key to its release. This evil force would be the main antagonist as it tries to break free and cause chaos in the ninja world. It could be something like a powerful demon that was once defeated by the first Hokage but is now on the verge of coming back because of the colossus contract. Naruto would have to stop it with the power of the colossus.
Well, it could be about Naruto making a unique contract with a colossus. Maybe the colossus has some special powers that Naruto needs to defeat his enemies. He might have to go through some tough trials to seal the contract.
It could be someone who is jealous of Naruto getting the monkey contract. Maybe a rogue ninja who wants the power for himself.
The main antagonist could be an ancient snake spirit that was bound to the contract. This spirit might not like the idea of Naruto, a human, having control over the powers of the contract. So it tries to possess Naruto or drive him insane by constantly whispering dark thoughts and trying to make him use the snake powers for evil. It would be a battle of wills between Naruto and this malevolent spirit.
A rogue ninja who wants to steal the power of the contract for his own evil purposes could be the main antagonist. He might be jealous of the connection between Sakura and Itachi and wants to break it to gain the abilities they could potentially unlock together.
It could be someone who wants to break their marriage contract for personal gain. Maybe a jealous ex - lover of Harry who doesn't want to see him with Tracey. This person could try to create misunderstandings between them and spread false rumors.
It could be someone from the Naruto universe who doesn't like Naruto's newfound fascination with Aku. For example, Danzo might see Naruto's interest in Aku as a threat to the stability of the village and try to stop Naruto from further exploring Aku - related things. So, Danzo could be the main antagonist in this case.
A group of rogue ninja who are hunting nekoshou for their special powers could be the main antagonists. They see Naruto's newfound connection with the nekoshou as a threat and try to eliminate him and the nekoshou he is protecting.
It could be a corrupt ninja from within the village who wants Naruto out of the way. Maybe someone jealous of Naruto's popularity and power, so they frame him and get him sent to prison. This antagonist would then try to keep Naruto in prison by any means necessary.
Madara Uchiha could be a great antagonist. His powerful Sharingan abilities and his grand plans for the Naruto world would put him at odds with Supergirl. He might see her as a threat to his control and try to manipulate or defeat her. Another option could be Kaguya Otsutsuki. Her god - like powers and desire to reshape the world would clash with Supergirl's values and her attempts to protect the people of the Naruto universe.
Maybe it's a ninja who has also been affected by Anodite magic but has turned to the dark side. This ninja could be jealous of Naruto's new powers and want to take them for himself. He would use his knowledge of both ninja techniques and Anodite powers to try and defeat Naruto.