"I am frustrated, I give up," she told the Swiss newspaper Blick in an interview published on Sunday. "I have written my letter of resignation and will send it in the next few days".
Del Ponte, a 70-year-old Swiss national who came to prominence investigating war crimes in Rwanda and the former Yugoslavia, has been part of the four-member UN Commission of Inquiry on Syria since September 2012.
The commission has been tasked with investigating human rights violations and war crimes in Syria since shortly after the conflict erupted in March 2011 with anti-government protests that have evolved into a complex proxy war.
Although the commission has released at least 12 reports on war crimes in Syria, investigators have never gained access to Syria itself.
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They have instead relied on nearly 4,600 interviews in the region and from Geneva, as well as pictures, medical records and other documents for their findings.
"I cannot remain on this commission that does absolutely nothing," Del Ponte told Blick, accusing members of the UN Security Council "of not wanting to establish justice".
"At first there was good and bad -- the opposition on the side of good and the government in the bad role," she said.
She added that she had never seen such crimes committed elsewhere, not in the former Yugoslavia or Rwanda.
Del Ponte, known for her frankness, has repeatedly voiced frustration at the lack of accountability for the horrendous crimes committed in Syria and has slammed the UN Security Council for "doing nothing".
She and the commission have also repeatedly urged the Security Council to refer the situation in Syria to the International Criminal Court.