Tshepo Motsepe (born 17 June 1953) is a South African physician and businesswoman.

In 2012, she completed a Social Entrepreneurship Certificate Program (SECP) at the Gordon Institute of Business Science.

[2] Motsepe has worked in both public and private practice in Mmakau, Mahikeng, Johannesburg, Pretoria, and in Zimbabwe.

Motsepe is married to Cyril Ramaphosa, President of the Republic of South Africa, with whom she has four children.

Her father is the late Chief Augustine Butana Chaane Motsepe, her brother is the mining magnate Patrice Motsepe, and her sister Bridgette Radebe, wife of African National Congress (ANC) politician and former Minister of Energy Jeff Radebe.