The New York Daily News said Cameron Douglas entered the plea in Manhattan federal court.
The charges stem from Douglas' July 2009 arrest after he allegedly mailed 215 grams of methamphetamine in a package addressed to a government informant's post office box.
He was first placed under house arrest, and then imprisoned after his girlfriend was allegedly caught attempting to smuggle heroin to him hidden in an electric toothbrush in August.
E! News said Douglas is expected to be sentenced to a minimum of 10 years in prison in exchange for his guilty plea.
His sentencing is set for April 27, E! News said.