Sen. John Glenn (D-Ohio) said today that President Reagan should "immediately serve notice" that anyone firing on U.S. Marines in Lebanon "will themselves become targets."

In a luncheon speech for the Foreign Policy Association, the Democratic presidential candidate said that the 1,200 Marines in Lebanon "are caught squarely in a crossfire," caused in part by a "drift in American policy" in the Mideast. The Americans, he said, should not be allowed to become "sitting ducks."

Glenn, a former Marine Corps colonel and fighter pilot, said that U.S. naval forces off the Lebanese coast should be allowed to assist the Americans and the Lebanese army in "any emergency situation such as saving the lives of our Marines."

Glenn also joined the growing chorus of Republican and Democratic leaders calling for Reagan to seek formal backing in Lebanon under the War Powers Act of 1973.

The speech was the second in a series on major issues that Glenn plans to give in coming months in an effort to spell out a platform for his presidential bid.

Much of it was pointedly directed at laying to rest suspicions among Jewish voters and contributors, a key voting block in this state, about his commitment to Israel.

He made his harshest attack yet on the Palestine Liberation Organization, charging that it has become "militarily irrelevant" and is in danger of becoming "politically irrelevant as well."

"The PLO has proven itself to be little more than a gang of terrorist thugs," he told the crowd of more than 500. "Until they abandon the use of terror and renounce forever their oath to destroy Israel, the U.S. should not recognize or negotiate with them."

Glenn also said the United States should move its embassy in Israel from Tel Aviv to Jerusalem when the Camp David negotiations are complete, or if they "irretrievably" break down.

Glenn has long been sensitive to accusations by the Jewish community that he favors bringing the PLO into Mideast negotiations. He has been trying for months to deal with this politically sensitive problem, which dates to remarks he allegedly made in 1979. At that time, he was quoted as saying that "The only way to get a final resolution of the Mideast situation is to get all the parties together, and that includes the PLO."

Beginning with a Feb. 14 speech to the National Jewish Community Relations Council, Glenn repeatedly has tried to reassure Jewish voters of his support for Israel, and his opposition to involvement with the PLO. He contends that some of his remarks have been misunderstood.

Some of Glenn's Jewish supporters have complained that there has been a defensive tone to his remarks, but today he took a more aggressive line. He said politicians often loudly trumpet their support for Israel as candidates but then use "evenhandedness" as a "convenient excuse to back away from their previous commitments."

"American commitment to a free and independent Israel must never fail, and never falter, for an hour, a minute or an instant," he said.

Milton A. Wolf, a Cleveland businessman and leading Glenn financial supporter, called the speech Glenn's "strongest and clearest" statement to date on Israel and the PLO. "His position has always been fine," Wolf added. "He just has not gotten the coverage his position deserves." Glenn's advisers said his remarks on Lebanon "tracked pretty well" with recent positions taken by Reagan. Glenn, however, partially criticized Reagan for not consulting with Congress or developing an overall Lebanon strategy.