Le Grand-Serre (French pronunciation: [lə ɡʁɑ̃ sɛʁ]) is a commune in the Drôme department in southeastern France.

The Galaure flows west through the northern part of the commune, then forms part of its north-western border.

The nearest communes are Marcollin and Saint-Clair-sur-Galaure, both in the Isère department.

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