The NDP were victorious in the election of 1999, and Friesen again scored an easy victory in her own riding. She was appointed Deputy Premier of Manitoba and Minister of Intergovernment Affairs on October 5, 1999, also receiving ministerial responsibility for Cooperative Development on September 25, 2002. Also in 2002, she defended the provincial government's controversial decision to spray malathion in the Winnipeg area, as a means of controlling the city's insect population during an outbreak of West Nile fever.
Friesen did not run for re-election in 2003, and formally stepped down from cabinet on June 25 of that year. She has subsequently returned to her teaching position at the University of Manitoba, and in 2004 issued a work entitled Magnificent Gifts: The Treaties of Canada with Indians of the Northwest, 1869-76.