Sant'Antioco is the name of both an island and a municipality (comune) in southwestern Sardinia, in the Province of Carbonia-Iglesias, in Sulcis zone. With a population of 11,730, the municipality of Sant'Antioco it is the island's largest community. It is also the site of ancient Sulci, considered the second city of Sardinia in antiquity.

Sant'Antioco is the second largest island of the region Sardinia, after Sardinia itself, with a surface of 109 km²; it is also the fourth in Italy after Sicily, Sardinia itself and Elba. It is located some 87 km from Cagliari, to which is connected through the SS126 state road, using a modern bridge. The island is divided between the two municipalities of Sant'Antioco and Calasetta. Other settlements are the small tourist resort of Maladroxia (a frazione of Sant'Antioco municipality) and Cussorgia, part of Calasetta.

The island of Sant'Antioco was settled at least from the 5th millennium BC (the so-called culture of San Michele of Ozieri), which was based mainly on fishing and agriculture. Typical tombs (called domus de janas) and menhirs belonging to this culture have been found. The island also housed nuraghe civilizations: findings include the nuraghe of Su Niu de Su Crobu ("Crow's Nest").