Smith played Cleo Martin in Love Soup (2005) and starred as Michelle, a hypocritical nutritionist, in three series of the sitcom Grownups (2006–2009). She has also appeared on The Lenny Henry Show as M.E. Westmocott, a role spoofing the various medical examiners on CSI. In the 2009 Two Pints of Lager Comic Relief special, which crossed over with Grownups, she played her characters from both series.
Smith played companion Lucie Miller alongside Paul McGann's Eighth Doctor in a radio series of Doctor Who, produced by Big Finish and transmitted on BBC 7 from New Year's Eve 2006; the plays returned in a second series released on CD and scheduled for BBC 7 broadcast. A third series of adventures for Lucie and the Doctor aired in March 2009, as weekly half-hour downloads followed by a Christmas Special. Lucie Miller made her final appearances in the fourth series, ending in 2011. She also narrated two Big Finish Short Trips stories, "The Curse of the Fugue" and "Flashpoint." Smith has reprised her role as Lucie Miller opposite McGann's Eighth Doctor in The Further Adventures of Lucie Miller, released in July 2019. Smith also appeared as Ruby Ruggles in the 2008 radio serial The Way We Live Right Now, and took over the role of Tamsin Trelawny in series 2 of Elephants to Catch Eels on BBC Radio 4.