Catherine Gladstone combined family responsibilities with charitable work and Liberal political organization. After marrying William Ewart Gladstone in 1839, she raised their children and helped sustain the household associated with Hawarden Castle. Her own activities increasingly extended beyond this household into work with vulnerable children and people recovering from illness.

During London's cholera epidemic of 1866, Catherine visited patients at the London Hospital and helped arrange care for children whose parents had died. She organized an orphanage at Clapton and raised support for country accommodation, subsequently associated with Woodford Hall. As the immediate need for cholera orphan care declined, the institution developed into a free convalescent home. She remained involved in selecting patients and securing help for people too weak to return directly to inadequate housing after discharge from hospital.

In 1887 Catherine became the first president of the Women's Liberal Federation, bringing her public standing to the organization of Liberal women across local associations. The federation expanded rapidly, although disagreements over women's suffrage later divided its members. Her presidency connected charitable experience and political networks with a growing role for women in party work. She continued to support her family through Gladstone's final years and survived him by two years. Catherine died in 1900 and was buried beside him in Westminster Abbey.