"We were never consulted about the ANC's approach to transformation and we do not accept it," De Klerk said at an address in Cape Town to mark 20 years of democracy.
"These policies...Are overtly directed against South African citizens on the basis of their race. That is unconstitutional and the antithesis of the goal of national reconciliation."
In 1993, De Klerk jointly received the Nobel Peace Prize with Mandela, three years after he freed the African National Congress leader who spent 27 years as a political prisoner.
De Klerk is now disillusioned with the ANC, calling for "serious talks" between the ruling party and all those affected by its transformation plans, which he said were based on racial discrimination.
"Not only has inequality increased throughout society, it has also increased within each of our population groups. Clearly, the government's policies to promote equality have failed," he said.
He highlighted the lack of adequate education and employment for all South Africans as the ANC's biggest failing, even as he acknowledged that in the Mandela era, the party was successful in addressing issues like providing housing, electricity, water and sanitation to 80 per cent of the population and extending social grants to over 16 million people.