The US president’s daughter-in-law, Vanessa Trump, was taken to hospital as a precaution after opening an envelope containing white powder, police say.
The letter was addressed to Donald Trump Jr, Mr Trump’s eldest son, at his apartment in Manhattan.
She and two other people at the scene were decontaminated by firefighters and taken to hospital for evaluation.
NYPD told the BBC they tested the white powder in the envelope and confirmed that it was non-hazardous.
They said that Mrs Trump did not appear to be physically affected by the substance.
The Secret Service is investigating.
The Fire Department of New York (FDNY) referred calls from the media to police, but confirmed that three people had been transported to the Weill Cornell Medical Center.
The call came to police at around 10:00 local time (15:00 GMT), according to local officials.
They said couple’s East 54th Street apartment was now being decontaminated.
In September, Mr Trump Jr, 40, chose to forgo Secret Service protection for himself, his wife and their five children, but it was reactivated one week later.
Donald Trump Jr, who works for his father’s business, married Mrs Trump (née Vanessa Kay Haydon) in November 2005 at the president’s Mar-a-Lago resort in Florida.
The wedding was officiated over by Mr Trump Jr’s aunt, the late Judge Maryanne Trump Barry.
Before marrying Mr Trump Jr, Mrs Trump worked as a fashion model in New York.
She had appeared in TV adverts and the film Something’s Gotta Give, starring Jack Nicholson and Diane Keaton.
The 40-year-old former Miss USA contestant once had a handbag company, La Poshett, which is now defunct.
Officials have been on alert for toxic substances sent through the mail since 2001 when anthrax was posted to lawmakers and journalists, killing five people.