Activist Mamphela Ramphele.
"When you're campaigning, you won't essentially be adding to the national debate, so I don't find it necessary to respond to all those in opposition to the ANC," Mantashe told the Mail & Guardian.
Mantashe was responding to comments made by Ramphele at the University of Cape Town's graduate school of business on Tuesday, where she claimed the ruling party "only loves power" and treated voters "like children".
"Come election time, it will appeal to you to vote for the party of Mandela, [it will] appeal to you to vote for the only liberation movement [and] appeal to you not to vote for the DA because they will take you back to apartheid," said Ramphele.
Ramphele added that South Africans were "given dummies" post 1994 and kept passive through social grants and programmes such as black economic empowerment.
"It's almost treating you like children and, unfortunately, we don't have civic education – where people understand that it is not possible to be taken back to apartheid.
"If you are poor and uneducated, you wonder if it is not possible that it can happen again," she said.
Ramphele cut her teeth as an apartheid activist while studying medicine at the University of Natal in the 1970s. She became increasingly involved in student politics and was one of the founders of the Black Consciousness Movement (BCM), alongside Steve Biko. She was specifically involved in organising and working with community development programmes through the BCM.
In 1975, she founded the Zanempilo Community Health Centre in Zinyoka, in the Eastern Cape – one of the first primary health care initiatives outside the public sector in South Africa.
Due to her political activities, she was banished to the town of Tzaneen from 1977 to 1984 by the apartheid government.
"If she wants to take an anti-ANC stance – that is hers to take. We've invited her to engage in governmental programmes but she's taken a view to work against the ANC," Mantashe said.
Mantashe also noted recent reports suggesting Ramphele was being courted by the opposition DA and hinted her comments are an indication she intends to enter active politics.
"If she wants to join the DA or form a political party, she will soon find out that it is no Sunday picnic," he added.
In February this year the City Press reported the DA was attempting to woo the struggle heavyweight as a possible successor to leader Helen Zille.
But Ramphele said at the time that she had never joined a political party in her life.
"I am not a joiner but a change agent. I have always seen my role as a change agent supporting any appropriate transformative process initiated by any South African," she said.
The DA said Ramphele was not a member of the party, when approached for comment by the M&G.
"We have no formal relations with Dr Ramphele. She has a personal relationship with Premier Helen Zille but that is where it ends," Mmusi Maimane, DA national spokesperson said.