Mrs Clinton arrived in Belfast on Friday morning, having spent the previous day in Dublin.
The visit comes after another night of trouble raged in the wake of Belfast City Hall's vote to stop flying the Union flag from the building all year round, and following the discovery of viable bombs.
The US Secretary expressed her distress over threats made to Alliance Party MP Naomi Long and attacks on the party's offices and councillors.
"There can be no place in the new Northern Ireland for any violence," Mrs Clinton said, during a press conference at Stormont Castle.
"The violence is a reminder that, although much progress has been made, the hard work of reconciliation and fostering mutual understanding must continue."
Ms Clinton, a long-time supporter of the peace process in Northern Ireland and of boosting the local economy through links with the US, also warned that international investment would be "impeded" by any return to violence on the streets.
She added that the US would stand in support of all those who worked towards maintaining peace.
There will always be disagreements in any democratic society - people have strong feelings. But you must not use violence as a means of expressing those strong feelings.
Mrs Clinton had been warmly welcomed at Stormont by First Minister Peter Robinson and deputy First Minister Martin McGuinness, who both thanked her for her support throughout the years.
Speaking later at a lunch at the £90m Titanic Centre, Ms Clinton said the peace process was being challenged and that political leaders must engage with grassroots politics.
"If we do not focus on a community level, on that interface, we will not have really achieved the peace that has been worked for," she said.
She said she would continue to work with politicians in Northern Ireland after she stands down as US Secretary of State next year.
She added: "Let us reach out to those who do not yet feel in their heart what has been achieved."
Ms Clinton met Alliance MP Naomi Long at the event alongside 500 guests including former First Minister Ian Paisley, 1972 gold medallist Dame Mary Peters and Nobel Peace Prize winners John Hume and David Trimble.
She was presented with a Worldwide Ireland Funds lifetime achievement award in recognition of her commitment to the peace process.
What we have to do is get out of the ballrooms, out of Stormont and into the communities where people live, where they do not have that lasting hope of optimism.
The visit is Mrs Clinton's eighth to Northern Ireland and her second as Secretary of State.
The last was in 2009 when she encouraged the devolution of policing and justice powers from London to Belfast.
Her return comes amid heavy security in the wake of the recent trouble.
A police officer was injured during disorder in the Linehall Street area of Ballymena when bottles, missiles and other masonry were thrown.
Two PSNI vehicles and two other vehicles were damaged and the window of a shop was smashed in the Co Antrim town, after an earlier protest took place.
Men aged 20 and 16 were arrested.
The disorder overnight follows a series of loyalist protests across Northern Ireland this week, some of which have targeted Alliance Party properties.
The party supported the proposals to only fly the City Hall flag on designated days.
DUP leader Peter Robinson has called for an immediate end to violence and the suspension of street protests.
Meanwhile the bombs have been made safe in Clough and Derry, where four men have been detained.