There's a possibility that it's a corrupted house - elf. This house - elf has been mistreated for a long time and decides to take revenge on the students. Using some dark magic that it has secretly learned, it casts the spell to turn them into Smurfs. The house - elf then hides in the shadows, causing more problems and trying to prevent Harry from reversing the spell.
Maybe a dark wizard from outside Hogwarts who has a vendetta against Harry. He targets Harry by creating a spell that not only turns the students into Smurfs but also has some other malicious effects. This wizard could be trying to use the chaos to steal some powerful magical artifacts from Hogwarts while everyone is distracted by the Smurf transformation.
It could be a jealous Slytherin student who manages to get hold of a powerful, cursed object. This object, when activated, causes the spell that turns students into Smurfs. So this Slytherin student would be the main villain as they try to disrupt Hogwarts and get Harry in trouble.
In this fanfiction, it could start with a strange experiment in the Potions class. Harry adds the wrong ingredient, which creates a magical mist that spreads through the classroom and turns everyone into Smurfs. The transformed students find that they have some of the characteristics of Smurfs, like being able to communicate with the forest creatures in a new way. Harry realizes that he has to use his knowledge of both wizardry and the newfound Smurf - like abilities to reverse the spell. He might encounter a Smurf - like version of Dumbledore who gives him some cryptic advice on how to break the spell.
One possible plot could be that the Smurfs accidentally find a magical portal that leads them to the wizarding world of Harry Potter. They could be initially confused but then start to explore. Maybe they meet Hagrid, who is fascinated by these small blue creatures. The Smurfs could use their unique skills, like Papa Smurf's potion - making skills, which could be a new and interesting concept in the wizarding world. And they could also get involved in some of Harry's adventures, helping him out in their own little ways.
It could be a new character created by the fanfiction author. Maybe a powerful wizard who was once shunned by the wizarding community and now wants revenge by stealing magic.
A dark wizard who has merged the dark arts with Wonderland's magic could be the main villain. He might have created some sort of dark Wonderland where all the creatures are under his control, and Harry has to break this control to restore balance.
Dumbledore could be the main antagonist. Harry might see Dumbledore as having used him all along for some grand plan. If Harry turns evil, he would want to break free from Dumbledore's influence. Dumbledore, with his power and wisdom, would then try to stop Harry from causing too much harm, thus becoming the main opposing force.
It could be Umbridge. If she discovers Harry's transformation into a veela, she might see it as something unnatural and try to use it against him. She could try to expel him from Hogwarts or make his life even more miserable than she already did in the original story.
Maybe the Ministry of Magic could be the main antagonist. If Harry turns into a hybrid, the Ministry might see him as a dangerous abomination. They could try to capture him and keep him locked away, thinking that his new form is a threat to the wizarding world's order. They might not understand that Harry is still the same person inside and that his new form could actually be an asset in the fight against evil.
It could still be Voldemort. Even if Harry is turning to the darkside, Voldemort might see him as a threat because Harry has his own unique power. Voldemort might not want to share his control over the dark forces with Harry, so he would become the main antagonist in a fight for dominance in the dark world.
Umbridge could also be a main antagonist. She is known for her strict and often cruel rules. If she discovers Harry in his female animal form, she would likely try to use it as an excuse to further oppress him. She might see it as a sign of abnormal magic and use it to justify her actions against Harry and those she doesn't like in Hogwarts.
Obviously, Harry and Hermione are the main characters. Harry is the one who undergoes the transformation into Hermione. Ron is also often involved as he is their close friend and his relationship with both Harry and Hermione is an important aspect. Dumbledore might also make an appearance as he is always aware of what's going on in Hogwarts and could play a role in either helping Harry deal with the transformation or in uncovering the cause of it.