She will star in The Effect, a play exploring neurology, sanity and the limits of medicine, BBC News reports.
The production has been written by Lucy Prebble, the playwright behind the West End hit ENRON, which George Clooney was previously said to be adapting for the big screen.
Piper's most recent on-screen appearance was in BBC One drama True Love, in which she played a secondary school teacher who falls for her female teenage pupil.
The former Doctor Who companion welcomed her second son with husband Laurence Fox in April.
The couple later confirmed that they had named the child Eugene Pip.