Sant'Ambrogio sul Garigliano is a comune (municipality) in the Province of Frosinone in the Italian region Lazio, located about 130 kilometres (81 miles) southeast of Rome and about 50 km (31 mi) southeast of Frosinone.

Sant'Ambrogio sul Garigliano borders the following municipalities: Rocca d'Evandro, Sant'Andrea del Garigliano, Sant'Apollinare.

During World War II, due to its position across the Gustav Line, it was mostly destroyed.

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