Mary of Guise was the mother of Mary, Queen of Scots, and second wife to Scotland's King James V. When she was widowed early, she became regent for her one-week-old daughter, Queen Mary.

Mary of Guise was the eldest daughter of Claude of Lorraine, Duke of Guise, a powerful French noble family, and his wife Antoinette de Bourbon. She married first at age eighteen, to Louis II, Duke of Longueville. The marriage was happy and she gave birth to a son. However, three years later, Louis died.

Mary was a widow at age twenty-one. Two months after her husband's death, she gave birth to a second son. The same year, Scotland's James V, who had lost his first wife, was looking for a new wife. He preferred French women, and as it happened, Mary of Guise strongly resembled his late wife. He was keen to wed her, but England's King Henry VIII was also interested, as he had recently lost his third wife, Jane Seymour, in childbirth. Mary was decidedly uninterested in Henry's suit, being well aware of how he had dispatched his first two wives (he divorced the first and beheaded the second). Additionally, the French king, Francis I, who had final say in who Mary would wed, did not care for Henry, and chose James instead.

Mary was not happy with James, either. She was reluctant to leave her country and had heard unpleasant things about life in Scotland. She acquiesced to her father's and the king's wishes and traveled to Scotland to marry James. The couple had two sons, neither of whom survived a year. Mary was their third child, who was born healthy and continued to thrive. King James died less than a week later, and the infant Mary was queen, with her mother, Mary, named as queen regnant. During her tenure as regnant, Mary had to negotiate multiple offers of marriage alliances for her infant daughter, and survive the difficult years of the Scottish Reformation.

As a Roman Catholic, Mary was strongly opposed to Protestantism, and when the Lords of the Congregation threatened to remove her and the baby Mary from power, she appealed to her royal French relations for assistance. Thereafter existed a tenuous, uneasy truce between the Catholic Scottish court and the nation's Protestant leaders. The truce continued for the better part of two decades, but at any time the country could have exploded in civil war. It is a tribute to Mary of Guise, English, Scottish, and French officials that peace continued to reign, with occasional skirmishes that were quickly brought under control.

By 1560, the Treaty of Berwick was signed, which allowed for the expulsion of the French from Scotland at last. Later that same year, Mary of Guise died, of dropsy, at Edinburgh Castle. She was taken to France for burial.