The cinematic adventure kicks off with a heartfelt warning from the Hero, portrayed by Chris Rock, directed to a group of curious children: “Witches are very real, and their wicked plans involve turning innocent kids into monstrous beings.” As the children take in a slideshow of haunting visuals, they are set for an adventure that will truly test their bravery.
We jump back to the Hero's childhood, where we find a young boy, played by Jahzir Bruno, grappling with the profound sadness following the tragic death of his parents in a car accident. Relocated to Alabama to be cared for by his nurturing Grandmother, portrayed by Octavia Spencer, the Boy becomes increasingly withdrawn, spending countless hours in his room, trapped in grief. Despite Grandma's best efforts to cheer him up, it isn't until she introduces a small mouse, named Daisy, into their lives that he starts to feel a spark of joy.
Their routine of healing together is disrupted when a strange woman begins lurking around their house, casting unsettling glances. With Grandma's health declining and coughing worsening, they venture into town, where the Boy has an alarming encounter with a cryptic figure known as Zelda, depicted by Josette Simon. Her uncanny voice and unsettling mannerisms send him rushing back to his Grandmother, who confirms the truth: witches are indeed real.
The Boy shares his troubling tale, and as his Grandmother, whose eyes twinkle with an inner knowing, recounts her own past, we learn about her childhood encounter with a girl named Alice Blue, played by [Ashanti Prince-Asafo], who tragically transformed into a chicken after taking candy from a stranger. This haunting memory prompts Grandma to secure her precious collection of herbal remedies and ancient books, revealing her deep awareness of the mystical and sinister forces that exist.
After leaving their cozy home for a temporary escape at a hotel, accompanied by their beloved dog Daisy, voiced by Kristin Chenowith, they face the challenge of sneaking her into the pet-free venue. However, an ominous vibe envelops the hotel as a coven of witches, led by the formidable Grand High Witch, played by Anne Hathaway, gathers. The meticulous hotel manager, portrayed by Stanley Tucci, is caught off guard by the arrival of Hades, the Grand High Witch's sinister cat, ultimately yielding to her requests.
In a twist of fate, the Boy befriends Bruno, played by Codie-Lei Eastick, another hotel guest. Bruno hints at a secret meeting with the enigmatic woman promising a mysterious treat. As the dark night unfolds, the Boy finds himself sneakily entering the witches' clandestine gathering, where he is horrified to witness their true, ghastly forms. The Grand High Witch harshly criticizes her followers for their failures but holds high hopes for a new potion that intends to transform every child into harmless mice.
In a shocking turn, Bruno arrives and consumes the promised candy, only to undergo a shocking transformation into a mouse. Alarmed, the Boy watches as Daisy springs into action to save him, but their escape is short-lived as the Grand High Witch retaliates, casting a spell that also turns the Boy into a mouse.
As the witches set out to capture these new tiny foes, Daisy skillfully leads the Boy and Bruno through the hotel’s complex ventilation system, avoiding capture through tight maneuvers. In a tense face-off, the mice narrowly escape, leaving the Grand High Witch frustrated and furious with claw marks from her unsuccessful attempts.
Once back in the safety of the Boy's room, Daisy and the Boy share their harrowing escape with Grandma, who is left reeling at the shocking revelation that her grandson has transformed into a mouse - a fate that Daisy similarly suffered a year earlier when she was transformed from a girl named Mary. Determined to protect her new family, Grandma resolves to create a plan to undo the spell.
Grandma hatches a clever scheme to steal a vial of the Grand High Witch's potion, hoping to create an antidote to restore her grandson's human form. Under cover of darkness, she disguises the Boy in a pouch and sneaks into the witch's lair. Just as they are about to be caught, the timely intervention of Mr. Stringer, distracted by Hades, allows them to escape unscathed.
Once back, Grandma experiments with her own potions to find a solution but realizes they cannot alter the effects of the witch's spell. Acceptance of their predicament, however, leads to a stronger emotional bond between Grandma and her mouse companions, who start feeling like her own family.
In a collective effort to fight back, the Boy, Bruno, and Daisy concoct a daring plan to sabotage the Grand High Witch. Under the cloak of night, the Boy stealthily pours the enchanted potion into a bowl of tasteless pea soup. The following morning, Grandma enters the dining area just as chaos ensues when the Grand High Witch gathers with her coven and begins to transform, turning her fellow witches into frightened rodents as hotel guests flee in terror.
In the midst of this mayhem, the mice take the chance to snatch the prized room key with the ominous number 666, symbolizing their rebellious stance. As they plot their next daring step, Grandma and her mouse companions make plans to rob the Grand High Witch of her stash of potions and treasures.
The climax draws near as the Grand High Witch confronts Grandma and the mice. Resourceful Bruno and Daisy seize the moment to outsmart the villain by activating mouse traps, leading to her anguished screams. Taking advantage of the distraction, the Boy launches himself forward, releasing a potion right into the Grand High Witch's throat, transforming her into a rat in the process. The ensuing chaos unleashes even further woe, as Hades finally has the upper hand against his former mistress, wreaking havoc among her ranks.
As the dust settles, the three successfully snatch the potions and treasures, with Grandma's attempts to reunite Bruno with his parents only leading to rejection, prompting her to adopt him along with Daisy. Despite the bittersweet nature of their situation, they cherish their time together, well aware of the fleeting nature of their lives.
Fast forward, the aged Hero, now sharing his tale with a fresh audience of eager children, reveals that he and Grandma have been rallying the youth to stand against witches. As Grandma queries the Hero if he’s ready to take on the mantle of the fight, he responds with determination, declaring that he has never felt more poised for the challenge ahead.
