Using her company's visibility and resources for social causes is a heartfelt priority. A member of CFDA's board of directors, Karan conceived and spearheaded its Seventh on Sale benefits to raise funds for AIDS awareness and education. Karan co-chairs the annual New York "Kids for Kids" events for the Elizabeth Glaser Pediatric AIDS Foundation, as she has since its 1993 inception, as well as underwrites "Super Saturday," an annual designer flea market/barbeque founded with the late Liz Tilberis in 1998 to benefit the Ovarian Cancer Research Fund. To facilitate her many on–going philanthropic involvements, in 1999, Karan and Weiss established the Karan Weiss Foundation.

Karan's Urban Zen initiative, founded in 2007, is the culmination of Karan's philanthropic efforts. Karan explains, "I have founded the Urban Zen initiative to create a working structure for advancing wellness, preserving culture and empowering children. These are causes that mean the world to me."