However she ruled out negotiations with the Palestinian group Hamas until it recognised Israel and renounced violence, saying her position on the issue was "absolute".
Al Jazeera's Rob Reynolds says that as Clinton's first session with the committee ended in Washington DC, a group of spectators shouted "ceasefire in Gaza" and held up signs.
Clinton also stressed the US must use "smart power" to further its foreign policy, with the military to be used as a "last resort".
"With 'smart power', diplomacy will be the vanguard of foreign policy," she told the senate foreign relations committee.
"America cannot solve the most pressing problem on our own and the world cannot solve them without America."
'Conflict' fears
Analysts say Clinton, currently senator of New York, is keen to strike a more pragmatic approach to foreign policy in an effort to distance the forthcoming administration of Obama, the US president-elect, from that of George Bush.
Clinton is expected to progress smoothly through the hearing, however some senators expressed concern that fundraising by her husband, former president Bill Clinton, could prove an ethical conflict of interest.
Richard Lugar, a senator and the panel's top Republican, said the Clinton Foundation could lead to foreign governments or businesses believing they could get preferential treatment through giving donations.
"It also sets up potential perception problems with any action taken by the secretary of state in relation to foreign givers or their countries," he said.
'Gravest threat'
 |
Clinton has faced criticism over previous
comments on Iran [GALLO/GETTY] |
Clinton said the "gravest threat" facing the US was the prospect of weapons of mass destruction falling into the hands of "terrorists".
She had harsh words for Iran and Syria, accusing them of "dangerous behaviour" and reiterating her position that "no options" were off the table regarding Iran, whom she said must end its "sponsorship of terror".
However, she said she was keen for the US to take a "new, different" approach towards the country diplomatically.
Clinton faced criticism during her battle with Obama for the Democratic presidential nomination over comments she made that the US would "totally obliterate" Iran if it attacked Israel.
She also urged a strengthening of ties with both China and Russia on "security and economic issues" and with Nato.