The FBI is investigating Mrs Clinton and her aides over whether they mishandled classified information on a private email server she used while serving as secretary of state.
Mrs Clinton denies handling classified information in her private emails.
She said she set up the email address for reasons of convenience, because it was easier to do everything from her Blackberry than to have several phones or tablets.
However, a state department inquiry accused her and other former US secretaries of state of poorly managing email security.
The justice department is now seeking to establish whether this constitutes a criminal offence.
Analysis: Laura Bicker, BBC News, Washington
Let’s face it – this is not really how you want to start a presidential campaign.
Hillary Clinton is trying to pitch herself as a sensible, qualified, experienced candidate who’s facing an outlandish controversial opponent in Donald Trump.
Being questioned by the FBI for three and a half hours is not going to help her case.
It gives her Republican opponents ammunition to describe her as untrustworthy. Mr Trump has already nicknamed her “crooked Hillary” and uses it with glee at every campaign stump speech.
The timing of this long-awaited interview is also interesting. This is a holiday weekend filled with Independence Day barbeques and parades. The Clinton campaign will hope that voters are more interested in where to watch the fireworks than the rolling network news coverage.