Her sympathy was roused by the sufferings of the Irish people during the famine, and she and her cousin, Eleanor Ewing, by their joint efforts, collected a large sum of money for their relief.

She went to Notre Dame, Indiana, to bid farewell to her brother who was there engaged in his studies for the priesthood, and there she met Edward Sorin, Provincial Superior of the Congregation of Holy Cross in the United States, through whose influence she was led to cast her lot with this small and struggling community.

She was then sent to France, where she made her novitiate at the convent of the Bon Secours Sisters, at Caen, making her religious profession by special dispensation on 8 December 1853, at the hands of the priest Basil Moreau, founder of the congregation.

When the Civil War broke out Gillespie organized a corps of eighty Sisters of Holy Cross to care for the sick and wounded soldiers.

[2] Four of the sisters were assigned to the USS Red Rover, the U.S. Navy's first hospital ship, which served the Mississippi Squadron until the end of the American Civil War.

[3] She established hospitals, both temporary and permanent, and, when generals failed to secure needed aid for the sick and wounded, she made trips to Washington on their behalf.

In 1869, at the advice of Bishop Luers of Fort Wayne, the Sisters of the Holy Cross in the United States determined on a separation from the members of the congregation in France.