He and his 2nd wife Anna of Prussia (1836-1918) had six children:
Prince Frederick William II of Hesse (1854–1888); never married; died at sea on a voyage from Batavia to Singapore.
Princess Elisabeth Alexandra Charlotte of Hesse (1861–1955); married Hereditary Prince Leopold Friedrich of Anhalt (son of Frederick I, Duke of Anhalt) and had issue.
Prince Alexander Frederick of Hesse (1863–1945); married Baroness Gisela Stockhorner von Starheim and had issue.
Prince Frederick Charles of Hesse, King of Finland (1868–1940); married Princess Margaret of Prussia and had issue. [Margaret and her family have a thread in the Hohenzollerns]
Princess Marie-Polyxene of Hesse (1872–1882).
Princess Sybille Marguerite of Hesse (1877–1925); married Baron Friedrich von Vincke (divorced 1923).
Emperor Franz Josef had wanted to marry Anna but she was already engaged to Friedrich. FJ's mother wrote to her sister, the Queen of Prussia, that "the happiness that showed itself to him like a fleeting dream and made an impression on his heart -- alas -- much stronger and deeper than I had first thought." She added "whether there is any hope that this sad marriage, which they are imposing on this charming Anna and which leaves her no prospect of happiness whatsoever, could be prevented..." So instead of becoming the Empress of Austria, she became the unhappy wife of Friedrich Wilhelm. In one biography--either Romanov Autumn or the Grand Duchesses--it is written how the marriage was doomed from the start since FW never got over the death of his first wife.