"We are seeing signals of a shift that truly alarms us all," the former Democratic presidential candidate told hundreds of students at Georgetown University in Washington.
"This administration's proposed cuts in international health, development and diplomacy would be a blow to women and children and a grave mistake for our country," said the Democrat, who ran the State Department from 2009 to 2013.
Trump wants to slash the US diplomatic budget by 28 per cent, although Congress will have the final say.
Clinton also pointed to the rise in the number of global refugees, and warned it is "not just somebody else's problem".
"I am pleading that our government will continue its leadership role on behalf of peace in the world," she said, "because the world must continue this work with or without US involvement."
Clinton said today's "complex and interconnected world" requires continued American leadership on multiple fronts, not merely a focus on one or two priorities.
"Will we be left behind or will we continue to lead the way?" she asked.
Clinton was at Georgetown to present awards in her name to four Colombians who helped advance the role of women in peace and security.
The former candidate and first lady received a warm welcome from the students, who chanted "Hillary! Hillary!" as she took the stage.
The 69-year-old former candidate offered a few jabs about the extraordinary 2016 presidential race, drawing extended applause when she said, "Here I go again, talking about research, evidence and facts".
She also mocked the phrase of a Trump advisor when she said stereotypes about women "belongs to the alternative reality".
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After her bitter defeat last November, Clinton largely disappeared from public view. When she took a selfie with someone she bumped into while walking in the woods outside her Chappaqua, New York home, the photograph went viral.
In the months since, she has emerged to attend Broadway shows, where she has received ovations and adulation from supporters.
She has also begun delivering speeches, including an address Tuesday at a businesswomen's conference in San Francisco where she criticized the shortage of women in Trump's inner circle, and pledged to keep speaking out about issues that matter.
"I am thrilled to be out of the woods, in the company of so many inspiring women," she said. "And there's no place I'd rather be than here with you - other than the White House."
