Medcalf will leave Albert Square in May, while Ryan's contract runs out in June. The news follows the axing of executive producer Kathleen Hutchinson, who worked on the show for just four months.
A BBC insider told the newspaper, "Kim's had a good time during her three years but feels she's gone as far as she can. The timing is pretty unfortunate as her screen mum Barbara Windsor has just agreed to come back. With Kathleen gone the new regime may try to talk her out of it."
Michelle Ryan has made no secret of her plans to leave the soap in recent months. Despite her character being at the centre of some of the show's biggest storylines, the actress is now considering a modelling career.
The insider added, "Michelle is hot property and has been inundated with offers of other acting work. She's also had several offers of lucrative modelling projects."
John Yorke and Tony Jordan have returned to the soap, as acting executive producer and story advisor respectively.
A source revealed, "Morale is high and already it feels as if the show is turning the corner. Losing very popular characters is obviously a blow - but if anyone can handle it well, John and Tony can."