A friend also told the Agence France-Presse news agency the 77-year-old had passed away.
"I can confirm that, unfortunately, Mira Markovic passed away," Milutin Mrkonjic, once a close associate of Milosevic and a family friend, said.
However, the Serbian Embassy in Moscow said it had no official confirmation of Markovic's death, Beta reported.
Read more: New trial for accused Serbian war criminals
Markovic, who fled Serbia in 2003 after being sentenced to a year in prison for abuse of office, was reported to have been in ill health in recent years. She, along with her son Marko Milosevic, was given political asylum in Russia in 2006 after fleeing her native country.
Milosevic's sweetheartShe and ultranationalist Milosevic, who ruled Serbia with an iron fist, were high school sweethearts, and she is credited with having a huge influence on the late strongman.
Markovic headed the left-wing JUL party, which in 1997 became his government's coalition partner.
After fueling a brutal ethnic conflict and mass murder across the Balkans following the breakup of the former Yugoslavia, Milosevic was ousted as president by a popular uprising in 2000.
He was later arrested and transferred to the United Nations war crimes court for the former Yugoslavia in The Hague, where he stood trial on charges of genocide, war crimes and crimes against humanity.
In 2006, four years into his trial, Milosevic died in his prison cell in The Hague from a heart attack.
Often dubbed the "Lady Macbeth of the Balkans," Markovic made considerable efforts over the years to clear her husband's name.
Read more: Serbia convicts ex-intel officers behind journalist assassination
The strongman's other sideThe former sociology professor released a lengthy autobiography defending the ex-Serbian president in 2015 and revealing how they fell in love.
The two-volume memoir described her husband as "the leading political figure" of the last decade of the 20th century.
At more than 900 pages, the book describes the couple's rise and fall, from when they met until Milosevic's death, as well as her childhood and her time in exile in Russia.
Markovic's own death comes a month after an appeal court in Serbia voided her one-year jail sentence and ordered a retrial.
She had also been named as a suspect in the mysterious assassination of former Serbian President Ivan Stambolic in August 2000.
Each evening at 1830 UTC, DW's editors send out a selection of the day's hard news and quality feature journalism. You can sign up to receive it directly here.