[7] She is a regular delegate to the World Economic Forum held in Davos,[8] as well as a member of the Harvard Kennedy School Women's Leadership Board.

[11] Born in Soweto, one of five siblings, her father was a teacher and her mother a nurse[12] She attended Wits University where she graduated with an MBBCh degree in 1987[13] and worked in the United States at the Medical College of Virginia in Richmond from 1991 to 1992.

[23] In 2015, she and her husband were honored by the Keep a Child Alive Foundation for their efforts addressing the issues of social and economic inequality of Africa's poorest people, and for their generous support of HIV and AIDS initiatives over the years.

[24] In 2017 she published The Precious Little Black Book to empower South African women with information about their rights, health and economic empowerment.

The donation, made at the outset of the COVID-19 pandemic, was allocated to assist with university sustainability, as well as the procurement of laptops and data for students to resume learning remotely.

[28] In 2023, through the Motsepe Foundation, she extended her support to all 26 South African universities through a R30 million donation for student registration, fees and historical debt.

[34] In 2017, she was the first recipient of the Franca Sozzani Award at the United Nations in New York for her efforts to promote African designers through her firm and support the empowerment of disadvantaged women.

[39] In sports, she has supported school-level athletics in South Africa through the Kay Motsepe Schools Championship, which includes football and netball competitions involving over 13,000 teams.