Simpson's third studio album, In This Skin (2003), was released the day that Newlyweds: Nick and Jessica premiered, with the show serving as a promotional tool for the record. In This Skin debuted at number ten on the Billboard 200, selling 64,000 copies in its first week of release. The album's opening numbers served as the lowest of Simpson's career at the time. In This Skin quickly declined the chart, and by January 2004 had sold just over 565,000 copies in the United States. Simpson released "With You" (2003) as the second single from the album in October. The single became a hit, reaching the top twenty of the Billboard Hot 100 and topping the Mainstream Top 40 chart based on radio airplay. Simpson performed during the halftime show of the Super Bowl XXXVIII. She recorded new material for a re-release of In This Skin, which was released in March 2004. The re-release dramatically aided in album sales; In This Skin went on to sell three million copies in the United States. Both "Take My Breath Away" (2004) and "Angels" (2004) were released as singles from the re-release.
Simpson and Lachey starred in the ABC special The Nick and Jessica Variety Hour in April, which featured guest appearances by celebrities such as Jewel and Mr. T, among others. That same month, she launched her Jessica Simpson Desserts by Jessica Simpson cosmetics line along with Randi Shinder; all of the products in the line were edible. Simpson embarked on her Reality Tour (2004) throughout North America beginning in June; the tour was a financial success, and ended in October. During this time, Simpson and her husband began making guest appearances on The Ashlee Simpson Show, chronicling the start of Jessica's sister's music career. Simpson's fourth studio album, a collection of Christmas themed songs titled ReJoyce: The Christmas Album (2004), was released on November 23. The album reached a peak of number fourteen on the Billboard 200, and was certified gold by the RIAA for sales exceeding 500,000 copies. Also in 2004, Simpson filmed a sitcom pilot for a ABC, which the network did not pick-up. In February 2005, Simpson and Shinder launched the Dessert Treats edible cosmetics line, similar to their prior line but targeted towards a younger audience. Both lines were canceled following a string of lawsuits.
Simpson is a registered Republican. She endorsed George W. Bush during his presidential campaign in 2004, though she canceled an appearance at a 2006 Republican fundraiser as she felt it was not "appropriate". Though a Republican, Simpson has praised former First Lady Michelle Obama during her husband's time in office, stating, "She's such an incredible woman, and she's with such a powerful man...Everything she does she exudes confidence."
In April 2004, Simpson performed during the VH1's benefit concert Divas Live 2004 alongside Ashanti, Cyndi Lauper, Gladys Knight, Joss Stone and Patti LaBelle, in support of the Save the Music Foundation. In May 2004, Simpson did a benefit concert to help the Skin Care Foundation. In March 2007, Simpson donated a new Chrysler minivan to the Elim orphanage in Nuevo Laredo. Simpson won a Chrysler Crossfire sports car at the 2006 MTV Video Music Awards, but exchanged the $50,000 luxury car for a minivan so she could help the orphanage. Simpson is Soles4Souls's Ambassador where she participated in autographing shoes to donate the money from communities across the United States. Simpson also works with Make A Wish Foundation.