Over 15,000 people marched through the UK capital, from Downing Street to the Israeli embassy in Kensington.
Sarah Colborne, director of the Palestine Solidarity Campaign, said: "London has already shown its outrage at Israel's attacks on the mostly refugee population of Gaza, with people turning out in their thousands last week.
"Today's national demonstration will give people from across the country the chance to say enough is enough: Israel's siege of Gaza and its occupation of Palestinian land has to end now.
"People want justice and freedom for the Palestinians, and they will be voicing this in their thousands."
Labour MP Diane Abbott addressed the crowds as they congregated around Whitehall.
"I am here to show solidarity with the people in Gaza," she said. "We call for an end to the occupation and justice for Palestinians."
Baroness Jenny Tonge, another of the speakers, said: "What on earth is Israel doing? It has lost its legitimacy, it is no longer a democratic state.
"It breaks international law, Geneva conventions, it has no respect for human rights. Israel must leave the international family of nations."
Organisers warned the crowd to spread out during the speeches for fears of being crushed because of the sheer numbers of people.
According to local reports, two children were pulled over a barrier close to the stage and one organiser said 10 people had fainted in the crowd.
Around 1,000 police officers will be policing the event from Whitehall to Kensington High Street.
More than 985 Palestinians, mainly civilians, have been killed since the launch of the Israeli operation, at the time of writing.
The UN warned of the "strong possibility" that Israel was violating international law and may be committing war crimes in Gaza.
The Israeli death toll stands at 39 soldiers and civilians.
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