Established as titulus S. Antonii in Campo Martio in 2001, it is currently assigned to Cardinal Manuel José Macário do Nascimento Clemente.

The hospice, with a small chapel dedicated to Our Lady of Bethlehem, had been founded in the fourteenth century by the noblewoman Guiomar of Lisbon.

The hospice later became the Istituto Portoghese di Sant'Antonio in Roma which sponsors, language classes, conferences, and concerts.

It includes Pietro Bracci's 1750 funerary monument of Manuel Pereira de Sampaio, Portuguese ambassador to the Holy See and Governor of Sant'Antonio dei Portoghesi.

A second monument, by Filippo della Valle, designed for the church is now at the Museu Nacional de Arte Antiga in Lisbon.