On 1 July 1862, Princess Alice married Prince Louis of Hesse and by Rhine (12 September 1837-13 March 1892), the son of Prince Charles of Hesse and by Rhine and the nephew of Louis III, Grand Duke of Hesse and by Rhine (9 June 1806-13 June 1877), at Osborne House on the Isle of Wight. On the day of the wedding, Queen Victoria issued Letters Patent granting her new son-in-law the style Royal Highness. This style was in effect in Great Britain, not Hesse.
Alice and Louis took up residence at Darmstadt, Hesse. The couple had seven children. It was later learned that Alice carried and passed on the haemophilia gene she inherited from Queen Victoria to several of her own children.
Princess Alice's concern about the poor nursing conditions for wounded soldiers during the 1866 Austro-Prussian War, led her to found the Alice-Frauenverein, or Women's Union, to train nurses and auxiliary workers. On 13 June 1877, Prince Louis succeeded his uncle as the reigning Grand Duke of Hesse and by Rhine and Princess Alice became the Grand Duchess. However, in November 1878, the Grand Duke and all but one of the children, Princess Elisabeth, fell ill with diphtheria; Princess Marie died of the disease. Exhausted by nursing all of them, Alice succumbed to the disease and died at the Neues Palais in Darmstadt on 14 December, the anniversary of her father's death. Alice is buried at Rosenhöhe, the mausoleum for the Grand Ducal House of Hesse outside Darmstadt.