Guise, a French noble family of the 16th and 17th centuries. It was founded by Claude of Lorraine (1496–1550). His chief possession, the county of Guise, was made a duchy by King Francis I in 1527, and Claude became the first duke of Guise.

Francis of Lorraine, second duke of Guise (1519–1563), and Charles of Guise, cardinal of Lorraine (1524–1574), sons of Claude, became very powerful in France during the reign of Francis II. Under the pretext of fighting against the spread of Protestantism, they and their followers attempted to gain control over the entire French kingdom.

Henry of Lorraine, third duke of Guise (1550–1588), son of Francis, became leader of the Catholic side in the French religious wars after his father's death. In 1576 he formed the Holy Catholic League, a union of Catholics organized to defend France against Protestantism.