Kim Kyong-hui has not been seen in public since stepping down from politics when her husband was executed by the regime in 2013.
Despite previous rumours the 71-year-old had died, it is now claimed she is being treated at a hospital in capital Pyongyang.
She is said to be suffering from illnesses including heart disease, cancer, dementia and depression.
The revelation was made by the National Intelligence Service in South Korea this week.
Ms Kyong-hui became one of the closest aides to the North Korean leader after her brother Kim Jong-il died in 2011.
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She was once thought to be untouchable in the country and was ranked as a general in the Korean People’s Army, one of the regime’s most prominent posts.
But she has not been seen in public for four years after her husband Jang Song-thaek was executed for allegedly plotting to overthrow the secretive regime.
Reports in North Korea said he had been fed to dogs or executed by firing squad.
A year later there were numerous reports of her death, either from suicide, a stroke or a heart attack.
In 2015 it was claimed that Mr Jong-un had ordered that she be poisoned.
It comes amid growing concerns about the nuclear capabilities of North Korea.
France has warned the communist state could even launch a nuclear attack on Europe.
The country’s foreign minister Jean-Yves Le Drian said: “The situation is extremely serious … we see North Korea setting itself as an objective to have, tomorrow or the day after, missiles that can transport nuclear weapons.
“In a few months that will be a reality.”
Tensions continue to escalate between North Korea and the United States.
Russian President Vladimir Putin warned today the standoff was close to spilling into a large-scale conflict and said it was a mistake to try to pressure Pyongyang into halting its nuclear missile programme.
Pyongyang has been working to develop a nuclear-tipped missile capable of hitting the United States and recently threatened to land missiles near the US Pacific territory of Guam.
On Monday, North Korea, which sees joint war games between the US and South Korea as preparations for invasion, raised the stakes by firing an intermediate-range missile over Japan.