During her Still Most Wanted tour, she performed in Guadalajara, Mexico, where she filmed a brief appearance on the soap opera Rebelde. She was also the guest star on The Andy Milonakis Show for its third season premiere in 2007. In April 2008, Duff was offered the lead role of Annie Mills in the CW Network's Beverly Hills, 90210 spinoff, but she turned it down because she was more interested in looking for projects outside the teen genre. She is also a model signed to IMG Models New York. Duff co-wrote the material for her third studio album Dignity, along with Kara DioGuardi, who co-produced the album with Rhett Lawrence, Tim & Bob and Richard "Humpty" Vission. Duff stated that compared to her previous music, it is "more dancey" and makes use of more real instruments. She said, "I don't know exactly how to explain what we're doing, but it's fun and funky and different, something new for me. It's really cool". She also described the album's sound as "a little less pop-rock and more electronic-sounding".

The first single, "Play with Fire", became a minor club hit but failed to chart in the U.S.; the second single, "With Love", was more successful, becoming Duff's biggest U.S. Hot 100 hit and topping the Billboard Hot Dance Club Play chart. The music video for "With Love" was used as a commercial for Duff's first fragrance, With Love... Hilary Duff, which was launched in September 2006; the video reached number one on Total Request Live. Initially slated for release in late 2006, the album was released in April 2007 in North America and earlier elsewhere. It reached the top five in the U.S. and Canada, the top twenty in Australia and the top forty in the UK. The Dignity tour began in mid-2007. A third single, "Stranger", was a number one U.S. club hit.

In early 2007, the Duff sisters lent their voices to the computer animated comedy Foodfight!, which is to be distributed by Lions Gate Films and scheduled to release in 2008. The director the film, Larry Kasanoff, said that he is "absolutely thrilled to have the Duff sisters as part of the cast". Duff also starred opposite John Cusack in War, Inc. which was released in theatres in Los Angeles and Manhattan, New York on May 23, 2008. Within a month of its release, it was expanded to several more theaters around the US. On September 7, 2007, Duff confirmed on Much On Demand, that she would be filming two independent films Greta, and Safety Glass. Both movies were filmed in late 2007 and are due to be released in late 2008 or early 2009. Duff has joined the cast of a new Polish brothers comedy Stay Cool. She will co-star alongside Winona Ryder, Mark Polish, Sean Astin, Chevy Chase and Jon Cryer. She will portray the character of Shasta O'Neil, described as a sexy high school senior. The movie was filmed during July and August 2008 in Santa Clarita, California, and the film is scheduled for release in 2009.

In January 2008, videos of Duff surfaced on YouTube, which showed her singing into her microphone at her concert in Mexico, but her voice was inaudible, leading viewers to believe that she was lip-syncing. Duff's representative defended her saying, "She was not lip-synching. It was faulty equipment. There was no sound coming out, but she was singing". He also added thatDuff was not using her regular sound equipment, but instead was using locally provided equipment and that her microphone was inadvertently set on mute for the first few minutes of the performance.

In November 2008, Duff's greatest hits album, Best of Hilary Duff was released but the album's first single "Reach Out" which samples Depeche Mode's "Personal Jesus" was released in the previous month. Duff thereafter announced that she would be leaving her record label Hollywood Records after six years of service. She later announced to MTV that she would begin work on her new album in December 2008. The same month, Duff signed a pact with NBC to star in a new series, thus signalling her return to the television medium.

• Stay Cool (2009) (post-production) .... Shasta O'Neil
• What Goes Up (2008) (post-production) .... Lucy
• Foodfight! (2008) (completed) (voice) .... Sunshine Goodness
• Greta (2008) (completed) .... Greta
• War, Inc. (2008) .... Yonica Babyyeah
• Material Girls (2006) .... Tanzie Marchetta
• Cheaper by the Dozen 2 (2005) .... Lorraine Baker
• The Perfect Man (2005) .... Holly Hamilton
• "George Lopez" .... Kenzie / ... (2 episodes, 2003-2005)
       - George's Grand Slam (2005) TV episode .... Kenzie
       - Team Leader (2003) TV episode .... Stephanie
• "Joan of Arcadia" .... Dylan Samuels (1 episode, 2005)
       - The Rise & Fall of Joan Girardi (2005) TV episode .... Dylan Samuels
• In Search of Santa (2004) (V) (voice) .... Crystal
• Raise Your Voice (2004) .... Teresa 'Terri' Fletcher
• A Cinderella Story (2004) .... Sam Montgomery
  ... aka Une aventure de Cendrillon (Canada: French title)
• "Lizzie McGuire" .... Lizzie McGuire (65 episodes, 2001-2004)
       - Magic Train (2004) TV episode (as Hillary Duff) .... Lizzie McGuire
       - Just One of the Guys (2003) TV episode (as Hillary Duff) .... Lizzie McGuire
       - My Dinner with Dig (2003) TV episode (as Hillary Duff) .... Lizzie McGuire
       - The Gordo Shuffle (2003) TV episode (as Hillary Duff) .... Lizzie McGuire
       - My Fair Larry (2003) TV episode (as Hillary Duff) .... Lizzie McGuire
        (60 more)
• "Frasier" .... Britney (1 episode, 2004)
       - Frasier-Lite (2004) TV episode (voice) .... Britney
• Cheaper by the Dozen (2003) .... Lorraine Baker
• "American Dreams" .... Shangri-Las (1 episode, 2003)