Seacrest worked with Burberry's Christopher Bailey who designed Seacrest's suits for red carpet events as well as New Year's Eve since 2009 and American Idol starting in 2010. Seacrest wore close-fitting suits and decided to make something similar for a wider audience at an "accessible" price point. With Bailey as his mentor, Seacrest developed his own collection, Ryan Seacrest Distinction, which launched in 2014. He formed an exclusive retail partnership with Macy's to sell the brand Distinction, consisting of suit separates, sports coats and evening wear manufactured by Peerless Clothing International. The line also includes accessories such as ties, pocket squares, belts, cufflinks and jewelry, which are manufactured by Randa Accessories. Seacrest works with Itochu for the production of dress shirts, as well as a sportswear collection released in September 2017.
In 2010, Seacrest launched the nonprofit Ryan Seacrest Foundation. The foundation has ten centers at Children's Healthcare of Atlanta, Children's Hospital of Orange County, Children's Hospital Los Angeles, Children's Hospital of Philadelphia, Children's National Medical Center, Levine Children's Hospital, Cincinnati Children's Hospital Medical Center, Children's Medical Center Dallas, Boston Children's Hospital and Children's Hospital Colorado. In April 2012, Seacrest named Selena Gomez as Ambassador to the Foundation. In February 2017, the foundation partnered with the Atlanta Braves to promote the non-profit at SunTrust Park. Seacrest did voice work for the Braves' "Welcome Home" broadcast media campaign.
In April 2010, Seacrest began dating Julianne Hough, a professional dancer, actress, and singer known for participating in Dancing with the Stars. On March 15, 2013, it was announced that their relationship had ended. They were dating for over two years before the split.