Charles de Lorraine, duc de Mayenne (26 March 1554 – 3 October 1611), or Charles de Guise, is a French nobleman of the house of Guise and a military leader of the Catholic League, which he heads during the French Wars of Religion, following the assassination of his brothers at Blois in 1588.

In 1596, when he makes peace with Henri of Navarre, the wars are essentially at an end.

He is the second son of Francis of Lorraine, Duke of Guise and Anna d'Este, the daughter of Ercole d'Este II, Duke of Ferrara and Renée of France.