Democratic presidential candidate Hillary Clinton, left, and Republican presidential candidate...

Democratic presidential candidate Hillary Clinton, left, and Republican presidential candidate Donal Trump in these 2016 file photos. Credit: AP

The Sept. 26 presidential debate at Hofstra University marks the first formal faceoff between Donald Trump and Hillary Clinton but also the first time in history that a man will go head-to-head against a woman in the high-stakes format.

Gender is very likely playing a role in how each White House hopeful prepares to handle the other, political experts agreed.

“It’s uncharted territory,” said Democratic strategist Bob Shrum, adding of the November campaign, “We’ve never, ever, ever had a woman in the presidential debates.”

The Republican nominee should be very conscious of how he attacks his Democratic opponent, Shrum said.

“I’m talking about calibrating the language that you use and the way you go after her,” said the politics veteran, who has prepped presidential contenders for debates.

Shrum and several others referenced the memorable 2000 Senate faceoff between Rick Lazio, then a GOP congressman from Brightwaters, and Clinton, who was first lady.

Lazio at one point crossed the stage and stood very close to Clinton, placing a campaign finance pledge on her lectern and jabbing at it while pressuring her to sign. She awkwardly shook his hand before he returned to his spot, still gesticulating at her.

The move was perceived as overly aggressive and chauvinistic, and experts said it sank his Senate prospects.

Trump will be civil toward his opponent, his campaign manager Kellyanne Conway told WNYM/970 AM radio host John Catsimatidis last month.

“When Secretary Clinton delivers her response, he will be respectful,” Conway said.

Republican consultant Susan Del Percio said whether gender limits how far the real estate magnate can push the envelope is a natural question.

“How you attack a man in a primary debate is different than how you attack the first female presidential nominee of a major party,” she said.

Clinton acknowledged last week that she believes “Women are seen through a different lens.”

The former secretary of state told Humans of New York, run by a photographer who takes portraits and posts them to social media with interviews, that she can’t express herself as a male politician would.

“They’ll be pounding the message, and screaming about how we need to win the election,” she said. “ . . . But I’ve learned that I can’t be quite so passionate in my presentation. I love to wave my arms, but apparently that’s a little bit scary to people. And I can’t yell too much. It comes across as ‘too loud’ or ‘too shrill’ or ‘too this’ or ‘too that.’ ”

Democratic consultant Alexis Grenell said it is Clinton who has to tread more carefully than Trump, for whom Grenell said the bar is very low.

“Even if she wanted to project anger or project outrage or project that she’s upset about something, she can’t do that,” Grenell said. “Because of the standard of what we consider acceptable for women to express publicly precludes anger, precludes emotion. The scrutiny for her is much stronger.”

Trump already has shared the debate stage with a female opponent this cycle, fellow GOP candidate Carly Fiorina, but he had a handful of other male primary contenders as buffers, experts said. Still, he was forced in a September debate to confront a comment he made to Rolling Stone about Fiorina’s appearance and separately chided her in a November contest for interrupting.

Trump has questioned Clinton’s health and stamina and earlier this month told ABC that she didn’t have a “presidential look.”

Shrum and Del Percio both said they think Clinton will be well-prepared for such personal criticism to come up at Hofstra.

Shrum predicted that Clinton won’t be explicit about the fact that she’s a woman unless Trump raises the topic first and will be bracing to strike back with “a killer line.”

Del Percio noted, “She’s been prepping and debating against the opposite sex for a generation.”

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