Sharik is a starving, scalded stray dog scraping by on the streets of 1925 Moscow. Deeply cynical about the working class who mistreat him, he initially views his rescuer with intense reverence. After undergoing a radical medical procedure, he transforms into a human and adopts a new name. He soon begins exhibiting crude, rebellious behaviors that challenge his master's authority.

Professor Preobrazhensky is an elite, bourgeois medical researcher specializing in lucrative rejuvenation surgeries for wealthy clients. Operating out of a spacious seven-room apartment that doubles as his clinic, he stubbornly resists the new Soviet housing mandates. He operates on Sharik with a sense of entitlement, expecting gratitude and submission while displaying deep contempt for the proletariat.

Doctor Bormenthal is Professor Preobrazhensky's devoted assistant and former student. Rescued from poverty by the professor, he harbors immense loyalty toward his mentor. He meticulously documents Sharik's progress in clinical notes and takes on a disciplinary role, becoming increasingly furious when the new household member threatens his master's peace.

Shvonder is the newly appointed leader of the apartment building's House Management Committee. As an ardent Bolshevik, he deeply resents the professor's bourgeois wealth and his ability to circumvent Soviet regulations. He actively attempts to enforce Communist housing policies and finds a willing, if unsophisticated, pupil in the newly transformed Sharikov.

Zina is the housemaid employed in Professor Preobrazhensky's expansive apartment. She assists with the daily management of the household and occasionally helps physically corral Sharik during his medical treatments. As Sharik adopts a human form, she frequently becomes the target of his false accusations and verbal abuse.

Darya Petrovna is the cook in Professor Preobrazhensky's household. She prepares the lavish meals the professor enjoys while the rest of the country faces food shortages. Her domain is the kitchen, where she initially rules over the stray dog, but she soon faces persistent harassment once the creature assumes a human form.

Fyodor is the doorman of the Obukhov Street apartment building. He provides the professor with updates about the new House Committee and the subdivision of the apartments. He maintains a respectful demeanor toward the wealthy professor and assists with practical building crises.

Pyotr Alexandrovich is a high-ranking local party leader and one of Professor Preobrazhensky's medical patients. He uses his political influence to protect the professor from the House Committee's expropriation efforts, illustrating the preferential treatment available to those with medical utility to the state.

Klim Chugunkin is a recently deceased petty criminal with a history of alcohol abuse. His physical materials are harvested by the medical team for experimental use, bringing his brutish, working-class traits into the professor's refined household.