Mantashe was reacting to recent statements made by Khoza attacking the ANC leadership.
Mantashe said he tried unsuccessfully to phone Khoza yesterday morning for him to explain his statement.
"Reuel Khoza must sell Nedbank and not venture into something he doesn't know. Wrong platform ... he has failed to sell Nedbank," Mantashe said.
Writing in his Nedbank's latest annual report, which was released on Friday, Khoza warned that South Africa's democracy was under threat from a "strange breed" of political leaders who appear to be incapable of dealing with the demands of modern-day governance and leadership.
Khoza seems to be responding to government's plan to review the judiciary, and to some leaders in the African National Congress who called for the Constitution to be reviewed as it hindered social and economic transformation.
"Our political leadership's moral quotient is degenerating and we are fast losing the checks and balances that are necessary to prevent a recurrence of the past.
"South Africa is widely recognised for its liberal and enlightened Constitution, yet we observe the emergence of a strange breed of leaders who are determined to undermine the rule of law and override the Constitution," Khoza said.
Mantashe advised Khoza to talk about business at Nedbank, not business he did not understand.