The church is vaulted, and lighted by four windows above a large cornice. That cornice, in turn, is supported by twelve pilasters, six on a side. There are four chapels in the church in addition to the main tribune. The main altar houses a tabernacle made from sardonyx agate, over which used to be placed an image of Our Lady of Humility by Pietro Perugino. That image, however, was lost sometime before 1814. When the chapel was transferred to the newly-formed American College, Archbishop Gaetano Bedini substituted it with a copy of the image of Our Lady of Mercy that is venerated in Rimini. This image is enclosed in an amethyst frame surrounded by a bas relief of four angels in gilded bronze. Two angels in white marble support the frame. The whole main altar was the work of Martino Longhi the Younger, who completed the work between 1643 and 1646. Sometime around 1859, it was moved away from the wall and raised to a higher level. Between the pilasters are six stucco statues of female saints: Cecilia, Catherine, Barbara, Agatha, Ursula, and Agnes. These statues are the work of Antonio Raggi and were sculpted and put in place between 1663 and 1674.