"They remind me a little bit of Hillary: No energy, no stamina, no strength!" he said of the protesters at one point.
The Massachusetts stop is part of his swing through New England to start the New Year, with rallies in New Hampshire and Vermont this week. It comes as Trump heads into the home stretch before the Iowa caucuses and New Hampshire primary.
Trump won big cheers while touting his opposition to the Iraq War and his argument the U.S. should "take the oil."
"For three years, for four years, 'Take the oil, take the oil, take the oil.' They never took it, now they want to take the oil. But I said take it and keep it and give some of it in terms of the form of money and profit to the veterans and the families," he said.
The crowd also erupted at his mention of Tom Brady, the New England Patriots star quarterback whom he is friends with.
"Tom Brady injured is still better than anyone else," he said, a nod to the player's recently hurt ankle. "I love him ... we have to get him better."
Trump also played to the region by acknowledging the horror of the Boston Marathon bombing and the heroin epidemic ravaging the northeast region.
While the Trump campaign estimated the crowd packed into the Paul Tsongas Center at the University of Massachusetts, Lowell, was 9,500 people, but the facilities staff at the center said it was just short of 7,000.
The crowd was as rowdy as any Trump rally, screaming out support throughout the speech. And though there were frequent interruptions by protesters, supporters adhered to the campaign's request to refrain from engaging in physical altercations.
Weeks ago, the campaign began airing a disclaimer before events asking supporters who spy protesters to point to them, begin chanting, "Trump, Trump, Trump," but not touch them. The new approach cut into Trump's talk throughout the night, though, as cheering supporters erupted, easily out-yelling the protesters themselves, as they were escorted out by police.