After his first full season at Feyenoord, Drenthe was called by Dutch under-21 coach Foppe de Haan to be part of his squad for the 2007 UEFA European Championship, which was held in the Netherlands.
On 14 November 2010, Drenthe was selected for the first time for the Dutch senior team, as coach Bert van Marwijk picked him as a late replacement for the injured Urby Emanuelson.