She has appeared in several films, including Elephant Juice (1999), written by This Life creator Amy Jenkins; Cargo (2004), and Festival (2005), a film comedy about the Edinburgh Festival. Although the film was not well received by critics and performed poorly at the box office, it was nominated for six Scottish BAFTAs. She also has extensive stage experience including the lead role in David McVicar's production of Camille at the Lyric, Hammersmith in 2003; Top Girls at the Citizens Theatre, Glasgow (2004) and Cue Deadly at the Riverside Studios (2004). In 2005, Nardini appeared in the title role in Etta Jenks at the Finborough Theatre, London. Between July and October 2009, she appeared in A Streetcar Named Desire at the Donmar Warehouse in London.
She appeared as Lady Huntly in the four-hour BBC epic Gunpowder, Treason & Plot in 2004, and played a shopaholic in Shiny, Shiny Bright New Hole in My Heart, again for the BBC, in 2006. Also in 2006, she reprised the role of Anna Forbes for the 10th anniversary reunion episode of This Life (This Life +10), which was shown on BBC Two in January 2007, and in November 2007, she read a story for Junior Jackanory on CBeebies. She appeared in an episode of the Inspector Morse spin-off series Lewis in 2008.
In 2007 Nardini played Servalan in B7 Productions Blake's 7 Audio adventures.
She played ruthless estate agent, Meredith McIlvanney, in the Annie Griffin comedy-drama New Town, shown on BBC Four in February 2009, for which she won a Scottish BAFTA. Other television appearances include Reckless (1997); Big Women (1998); Undercover Heart (1998); Love in the 21st Century (1999); Tube Tales (1999); Rough Treatment (2000); Sirens (2002); Outside the Rules (2002) and Quite Ugly One Morning (2004).
In Late November 2012, Daniela Nardini joined the cast of BBC One’s award-winning drama Waterloo Road for the third instalment of its eighth series, filming on location in Greenock, Scotland. Daniela’s character, Esther Fairclough, is a passionate, driven but maverick science Teacher who has an unconventional approach to inspiring her pupils. Daniela says: "Esther is mildly dangerous with the potential to get more so. She is passionate about her cause but unfortunately doesn't know how to encourage and promote her views without getting carried away."
Nardini plays Chris Guthrie's mother in the 2015 film of Sunset Song.
