The pro-Palestinian rally began at 5 p.m. Friday at Columbus Circle, with thousands marching through the streets to demand an overseas ceasefire.
Protesters then headed to the New York Times building, vandalizing the facade with a red tint before heading toward Grand Central.
LIRR and Metro-North services were also disrupted.
Police have made several arrests, but do not have an exact number.
Around 1,500 demonstrators in New York demonstrated in the streets Thursday evening to call for an end to the war in the Middle East.
The rally took place after students from several schools also walked out of class to call for a ceasefire in the war between Israel and Hamas.
The protest in Midtown, organized by pro-Palestinian groups, called on people to leave school or work for a citywide shutdown.
Last October, more than 300 people were arrested after peace activists gathered inside Grand Central Terminal on Friday evening to call for a ceasefire in Gaza.
The protests forced the MTA to restrict access to Grand Central.
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