Abandoned by their father deep in a forest, young Hansel and Gretel enter a gingerbread house and are captured by an old witch. The witch forces Hansel to continuously eat candy while making Gretel prepare the oven, but the siblings outsmart her and incinerate her in the fire of the oven. In the fifteen years that follow, Hansel and Gretel become famed witch hunters, slaying hundreds of witches. The pair find that they are somehow immune to spells and curses, but the incident in the gingerbread house has left Hansel diabetic. He needs a shot of insulin every few hours or he will get sick and die.[N 1]
Hansel and Gretel arrive in the town of Augsburg and immediately prevent Sheriff Berringer from executing a young woman named Mina for witchcraft. Mayor Englemann tells the crowd that he has hired the siblings to rescue several children presumed abducted by witches. Berringer hires trackers for the same mission in the hopes of disgracing the mayor and cementing his power. All but one of the sheriff's party are killed that night by the powerful grand witch Muriel, who sends one man back to the town tavern as a warning to the locals. Hansel and Gretel, along with the Mayor's deputy Jackson, capture one of Muriel's witches and interrogate her. They discover that the witches are preparing for the coming Blood Moon, where they plan to sacrifice twelve children in order to gain an immunity to fire. Muriel, accompanied by her witches and a troll named Edward, attack the town and abduct the final child. Muriel kills Jackson and launches Gretel out a window, rendering her unconscious. Gretel is rescued by Ben, a local teenager who is a fan of theirs and plans to be a witch hunter himself. Hansel grabs onto a fleeing witch by her broomstick, but falls and is lost in the forest.
The next morning, Hansel is found hanging from a tree by Mina. She takes him to a nearby spring where she heals his wounds and makes love to him. Gretel searches for Hansel in the forest but is attacked by Sheriff Berringer and his posse. The men capture and beat Gretel before being stopped by Edward, who kills the sheriff and his men. Edward tends Gretel's wounds and tells her that he helped her because trolls serve witches. Hansel and Gretel reunite at an abandoned cabin, which they discover is both a witch's lair and their childhood home. Muriel appears in front of them, telling them the truth of their past. She reveals that Hansel and Gretel's mother was a grand white witch named Adrianna who married a farmer. On the night of the last Blood Moon, Muriel planned to use the heart of the white witch to complete her potion. She found Adrianna too powerful and decided to use Gretel's heart instead. To get rid of Adrianna, Muriel revealed to the townspeople that Adrianna was a witch. The townspeople burned her alive and hung Hansel and Gretel's father. Following this revelation, the siblings battle Muriel before she stabs Hansel and abducts Gretel for the ceremony.
Hansel wakes up with Mina, who reveals herself to be a white witch. She heals his wounds again and uses a grimoire to bless Hansel's arsenal of weapons. Hansel, Mina, and Ben head out to disrupt the Blood Moon Sabbath. Mina begins slaughtering dark witches with a Gatling gun, while Hansel squares off against Muriel's witches and frees the children. Edward defies Muriel's orders and releases Gretel before Muriel throws him off the cliff. Muriel flees on a broomstick, but Ben manages to shoot her and forces her to crash. Hansel goes after Muriel while Gretel stops to revive Edward. Hansel, Ben, and Mina follow Muriel's trail to the original gingerbread house. Muriel wounds Ben and kills Mina before Hansel shoots her several times, knocking her into the house. Gretel arrives and the pair engage Muriel in a brutal fight that ends with Muriel being beheaded with a shovel. They burn Muriel's body on a pyre and collect their reward for rescuing the children.
Hansel and Gretel head out on their next witch hunt accompanied by Ben and Edward. Before the credits roll, Hansel and Gretel are seen taking down a sand-powered witch.