Police are looking for others who might have survived Tuesday's crash off the country's southern coast, said Maj. Gilberto Delgado Valdez with the National Drug Control agency.
He said authorities on land and at sea were tracking the plane, whose pilot was expected to air drop the drugs but likely decided to set down on the water, possibly because the plane ran out of fuel.
It is the third reported plane accident tied to drug-trafficking in recent months.
In May, a burned plane was found in the country's eastern region, and another plane laden with cocaine crashed last year, killing its four occupants.
The Dominican Republic is among the top 20 producers or transit sites for illegal drugs, according to the U.S. State Department.