Mattis's visit, his second to the region, is the latest in a string of appearances by top US officials who have scrambled to reassure partners about US commitments.
While campaigning, Trump sparked broad anxiety by calling into question long-standing security assumptions and mutual defence treaties with Japan and South Korea.
But the US leader's views have shifted since he took office, and Mattis told reporters he would be underscoring American support for the region.
Mattis will deliver his message at a policy speech at the Shangri-La Dialogue on Saturday.
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The summits have in recent years been dominated by concerns over China's rapid build up of islets and maritime features in the South China Sea, where Beijing has reclaimed thousands of acres of land and installed military fortifications.
The issue remains front and center, but this year the focus is also on North Korea and its accelerating push to develop an intercontinental ballistic missile.
Since taking office, Trump, who laced his campaign rhetoric with anti-China sentiment, has made an about-face and turned to China to apply pressure on North Korea to rein in its nuclear weapons program.
After meeting with President Xi Jinping in April, Trump, who once accused China of "raping" the US, praised its leader as a "good man", saying it would be inappropriate to pressure Beijing while Washington is seeking its help with Pyongyang.
"There's concern over China's rise and it's assertive behaviour, particularly in maritime space," said David Helvey, a top Pentagon advisor for Asian and Pacific security affairs.
"And there's also questions about where the United States is going to be in the Asia-Pacific region in the new administration."
Mattis's challenge is to reassure allies that America can apply pressure on China over the South China Sea, while at the same time convincing Beijing that controlling North Korea is in its own security interests.
Underscoring the point, the US Navy on May 25 conducted a "freedom of navigation" operation in the South China Sea, when the USS Dewey guided-missile destroyer sailed within 12 nautical miles of Mischief Reef in the Spratly Islands.