The Guadiana (Spanish pronunciation: [ɡwaðiˈana], Portuguese: [ɡwɐðiˈɐnɐ]), or Odiana, is an international river located on the Portuguese–Spanish border, separating Extremadura and Andalucia (Spain) from Alentejo and Algarve (Portugal). The river's basin extends from the eastern portion of Extremadura to the southern provinces of the Algarve; the river and its tributaries flow from east to west, then south to the border towns of Vila Real de Santo António (Portugal) and Ayamonte (Spain), where it flows into the Gulf of Cádiz. With a course that covers a distance of 829 km, it is the fourth-longest in the Iberian peninsula, and its hydrological basin extends into an area of approximately 68,000 km² (the majority of which lies within Spain).

The Romans referred to the river as the Anas, from the Latin "Flumen Anas", which means "of/or pertaining to ducks". During the Moorish occupation and settlement, the name was extended and referred to as Uádi Ana (uadi being the Arab term for river), later passed on to Portuguese and Spanish settlers as the Ouadiana, and later just Odiana. Since the 16th Century, due to Castilian influences, the name has slowly evolved to taken on the form Guadiana, a cognitive variation that developed from many Moorish-Arab river place-names using the prefix guad (such as the rivers Guadalquivir, Guadalete, Guadalajara or Guadarrama). There is controversy about the exact source of the river in Castilla-La Mancha (see Lagunas de Ruidera). The river flows east to west through Spain, then it flows south through Portugal. It flows into the Gulf of Cádiz, part of the Atlantic Ocean, between Vila Real de Santo António (Portugal) and Ayamonte (Spain).