The event, organized by the Palestine Solidarity Campaign, began at Russell Square in the city center before attendees marched to Trafalgar Square for a mid-afternoon rally.
A smaller number of demonstrators also turned out for a counter-protest in support of Israel, with lines of police separating the two gatherings.
London has seen numerous large-scale pro-Palestinian protests since Israel mounted its military response to Hamas's unprecedented attack on October 7, as well as smaller pro-Israel counter-demonstrations.
The rallies for Palestinians have proved contentious, attracting criticism for fuelling a hostile environment towards Jewish people. Some ruling Conservative lawmakers have branded them "hate marches."
FILE— A protester holds a shroud reading "Children of Gaza" as pro-Palestinian activists and supporters gather for a protest in central London on March 30, 2024, calling for a ceasefire in the Israel/Hamas conflict.
Police have made dozens of arrests over those months for anti-Semitic chanting and banners, promoting a proscribed organization and assaulting emergency workers.
That included on Saturday, with officers making four arrests for hate crime, public order and terrorism offences.
A man was detained for the terror-related offence related to "inviting support for a proscribed organization," London's Metropolitan Police said.
Organizers have insisted throughout they are exercising their democratic rights and that law-breakers make up a tiny minority of the sometimes tens of thousands of people who have turned out.
Sally Worgan, 65, a retired social worker, had traveled from Gloucestershire in western England to attend.
"I think it's important for the Palestinian people to know that people do support them, that they're not just on their own," she told AFP.
"We will keep marching," Ben Jamal, one of the organizers, told Sky News on Saturday, adding attendees wanted "a permanent ceasefire" and more aid to be delivered to Palestinians in Gaza.
"We already know that 70 percent of the British public according to opinion polls support the demands that we're making."
The Met said in the build-up to Saturday that it had "a robust policing plan in place," including requiring marchers to keep to a pre-approved route and disperse by 5:00 pm (1700 GMT).
Deputy Assistant Commissioner Andy Valentine, who oversaw the policing operation, said it had been an "extremely busy" day, with several other events taking place across the capital.
"I have been clear in my intention for this weekend that we will not tolerate anyone who is intent on carrying out criminality or causing any form of disorder or anti-social behavior," he added in a statement.
Prime Minister Rishi Sunak earlier this month called for officers to take tougher action against protesters at such events, saying they "had descended into intimidation, threats and planned acts of violence."