During the fierce offensive to oust the IS group from its former stronghold Raqa, Syrian Democratic Forces (SDF) have captured "hundreds" of foreign jihadists, Mattis said.
The United States does not want the prisoners to remain in Syria where they fear the power vacuum could allow the fighters to escape and once again take up arms.
They say foreign fighters should be to be dealt with in their country of origin.
"It is an international problem, it needs to be addressed by all engaged."
But several countries do not want the jihadists to return home.
Two Britons said to have carried out numerous beheadings are among the detainees.
Alexanda Amon Kotey and El Shafee el-Sheikh -- suspected members of a jihadist cell known "The Beatles" because of their British accents -- are accused of abducting and decapitating around 20 hostages.
"I don't think they should ever set foot in this country again," Britain's Defence Secretary Gavin Williamson recently told the Sun daily newspaper.
The question of whether the detainees could be imprisoned at US military's Guantanamo Bay prison was raised, but when asked directly for an answer Mattis declined to comment.
The US Secretary of Defence now travels to Brussels for the second-leg of his European visit dedicated to the anti-jihadist fight.
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