The 84-year-old former general, nicknamed the Butcher of Bosnia, had been in ill health in the last few years and was hospitalised repeatedly.
He had been in the United Nations detention centre since his arrest in 2011.
The media reports said that Mladic died in a UN prison hospital in the Hague, Netherlands.
A family member of Mladic, who spoke on condition of anonymity because of the sensitivity of the situation, confirmed the reports and said Mladic's son Darko Mladic was on the way to the Hague.
The UN tribunal for war crimes committed during the wars in Yugoslavia in the 1990s sentenced Mladic to life in prison in 2017 in what was considered a key step toward bringing justice to the victims.
He had been in custody since 2011 after many years on the run.
The ruthless, blue-eyed former communist officer-turned nationalist warlord, was one of the most notorious figures of the conflict that left more than 100,000 people dead and a million homeless.
When the ethnic war in Bosnia started in 1992, Mladic became the commander of the Bosnian Serb troops and took control of large swaths of the country to form a Serb mini-state.
Serbian forces under Mladic's control laid siege to the capital Sarajevo and other cities and villages, established camps for detained non-Serb civilians and enemy soldiers and systematically killed prisoners.
with Reuters
