Dr Salvador Plasencia, and Jasveen Sangha, whom authorities said was a drug dealer known to customers as the "ketamine queen," have pleaded not guilty to charges related to the October 2023 death of Perry.
An autopsy determined that the 54-year-old died from "acute effects" of ketamine and other factors that caused him to lose consciousness and drown in his hot tub.
Ketamine is a short-acting anesthetic with hallucinogenic properties, sometimes prescribed to treat depression and anxiety but also abused by recreational users.
Perry had publicly acknowledged decades of substance abuse, including during the years he starred as Chandler Bing on the hit 1990s television sitcom Friends.
Plasencia and Sangha are scheduled be tried together in federal court in Los Angeles starting on March 4.
Three other defendants have agreed to plead guilty in connection with Perry's death.
