Gregory is an elderly anthropomorphic mouse managing Gregory House, a mysterious hotel in an alternate dimension serving as purgatory for lost souls. He appears as a grey-furred rodent with purple irises, a creased forehead, visible eye bags, facial warts, and faded blonde shoulder-length hair. He typically wears a pink trench coat over a black-and-red striped shirt, often carrying a brass candle holder with a wax candle or a set of keys.

His primary role involves trapping guests to erode their sanity and capture their souls, which he delivers to his mother, Gregory Mama, for her revitalization. Gregory demonstrates a deep-seated fear of this mother, whom he loathes but obeys out of terror. Despite his antagonistic actions, he maintains a superficially polite demeanor, addressing guests as "my friend" (to males) or "my dear" (to females). He appears unexpectedly to deliver unsettling remarks or philosophical musings on desire, regret, and the nature of reality, punctuated by a menacing chuckle. He exhibits a perverse sense of humor and possesses a collection of pornographic magazines hidden in the hotel storeroom.

Gregory employs psychological methods, identifying and exploiting emotional weaknesses in his guests while refusing to intervene when other residents torment them. This aligns with the implication he may be an anthropomorphic personification of suppressed human desires or a spirit of dreams and desires, manifesting as an escape from mundane reality. He displays a compulsive need to control guests' whereabouts and actions, reflecting his role as dimension lord over this chaotic purgatory. Functionally immortal and inescapable, Gregory and the hotel resurrect even after destruction (like Neko Zombie's arson in "The Second Guest"), ensuring a guest's room remains perpetually ready for their inevitable return.

Across storylines, Gregory's character shows nuanced development. In "The Last Train," he becomes a protagonist seeking escape, offering advice to fellow passengers about defying fate while cynically observing their failures. Here, he articulates a belief in self-determination and chaos over predestination, opposing Judgment Boy's philosophy. In "The Bloody Karte," he is a recurring patient in Catherine's hospital, enduring physical abuse from his mother and others, casting him more sympathetically and comically. The manga reveals he collects bizarre artifacts (e.g., a Russian roulette chair, Hitler's dentures), a childhood hobby, and exhibits moments of genuine camaraderie with guests despite manipulative goals.

His relationship with grandson James involves frustration and occasional concern, especially when James's mischief interferes with Gregory's schemes. Gregory harbors bitter enmity toward Neko Zombie, a feline resident he mutilated and imprisoned as revenge against cats, whom he considers dangerous. His defining moment occurs in "Soul Collector," where he schemes to trap the player character's soul for his mother. When the player foils this and escapes, Gregory transforms into a spectral form to plead, then demand their return, culminating in a desperate villainous breakdown as they reject his purgatory. Despite this failure, he ultimately resurrects with the hotel and welcomes the player back.