"I'm really here to listen to what your experiences have been," Clinton said during the meeting.
She noted that the attack on the gay club highlights the dangers that LGBT people in America face, including higher risk for hate crimes.
"We need to acknowledge and be very clear who this attack targeted," Clinton said. "The Latino LGBT community by any measure was the community that was the most severely impacted by this terrible attack."
"It is still dangerous to be LGBT in America," Clinton added. "It is an unfortunate fact but one that needs to be said."
The meeting comes on a day when much of the political world is returning from the Republican National Convention and speculation is swirling about whom Clinton will choose as her vice president.
She is expected to unveil her choice in a text message to supporters and appear with the vice-presidential candidate at a campaign event in Florida this weekend.
But at the meeting, the mood was somber. Clinton entered from a side door to a virtually silent room.
Some members of the community — still reeling from the tragedy — offered thanks for her decision to wait until several weeks had passed before traveling to the city.
"Thank you for not politicizing it and for waiting until we were ready," said Patty Sheehan, an Orlando city commissioner.
Sheehan said she considers the LGBT community in Orlando to be like her children.
"It felt like they came into our living room and shot them," Sheehan said.
But she cautioned against blaming the Muslim community for the attack because the gunman, a Muslim who was the son of an Afghan immigrant, had apparently been self-radicalized, and according to law enforcement officials, had pledged allegiance to the Islamic State.
"Hating a Muslim person is the same as hating a gay person," Sheehan said, growing emotional. "We cannot allow this country to become a country of hatred and division."
"We have got to stop this kind of rhetoric. We are better together," she added.
As she did after the attack, Clinton on Friday called for "sensible gun control." And she added that it also highlights the need to combat radicalization online.
"We still have to take on the epidemic of gun violence," Clinton said. "Second, we have to disrupt and dismantle the global online network that radicalizes people here in the United States."
Later, Clinton left flowers at the memorial for the shooting victims outside of the shuttered nightclub. She was joined by Sen. Bill Nelson (D-Fla.) and first responders.