UN spokesman Stephane Dujarric said the secretary-general also called for prompt action to facilitate their safe return to their families.
Israeli defense officials identified one of the men as Avraham Mangisto, an Israeli of Ethiopian descent in his late 20s who disappeared after he "independently" entered Gaza on Sept. 7, 2014, two weeks after the end of Israel's war with Hamas.
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Israel said the second man was a Bedouin Arab citizen from southern Israel but refused to identify him or say how long he had been in Gaza or how he got there.
Dujarric said "the secretary-general underscores the responsibility of all parties to protect and respect the rights of civilians."
He said the United Nations will continue to closely monitor developments.
Last week's announcement that the two Israelis are missing brought back bitter memories of the case of Israeli soldier Gilad Schalit, who was captured and imprisoned for five years by Hamas.
But circumstances have changed dramatically since Schalit's release in a 2011 prisoner swap. Israeli observers say what happens to the two missing civilians could provide an important test of a new fragile detente that has emerged between Israel and Hamas since last year's devastating war.
Israeli Prime Minister Benjamin Netanyahu said last week he held Hamas, which has ruled Gaza since 2007, responsible for the fate of both men. He said Israel is working to free them.