After the death of her husband in August 1982, the Royal Congress named Dzeliwe as Queen Regent, until Prince Makhosetive, designated by the king as his successor, reached the age of twenty-one. The Liqoqo supported her regency, but soon there were disagreements between her Prime Minister, Mabandla Dlamini, and other members of Congress led by Mfansibili Dlamini. These problems continued until March 1983, when Prince Mabandla was replaced by Prince Bhekimpi Dlamini. Queen Dzeliwe opposed this dismissal, and this led to her being replaced by the mother of Makhosetive, Ntombi of Swaziland as regent.
In May 1987, twelve people were accused of sedition and treason in relation to the overthrow of Queen Regent Dzeliwe in 1983. King Mswati created a special tribunal to judge these crimes against the King or the Queen Regent, in which the defendants did not have the right to legal representation. In March 1988, they were prosecuted by the tribunal, although they were set free in July.
Between 1981 and 1985, she maintained the post of Joint President of the National Congress.