The main collection is displayed in state rooms, including the chapel, complete with the mummified corpse of the family saint.

The palace was renovated for the marriage of Andrea IV Doria Pamphilj Landi to Princess Leopoldina Maria of Savoy, daughter of Louis Victor, Prince of Carignan, and Christine of Hesse-Rotenburg in 1767.

Diego Velázquez's Portrait of Innocent X (previously Cardinal Giovan Battista Pamphilj, who became Pope in 1644) is considered to be the collection's masterpiece.

Velázquez, while not idealizing the Pope's countenance, is not unflattering in the portrait; Innocent X's features were believed by his contemporaries to symbolise a despotic lifestyle and vindictive character.

The portrait painted to commemorate the Holy Year was commissioned by his hedonistic sister-in-law Olimpia Maidalchini, who was his close confidante and adviser, and some say mistress.

Following a period of exile in the country, to avoid confrontation with the Pope and Olimpia Maidalchini, the newly married couple took up permanent residence in the Palazzo Aldobrandini, which from 1654 Camillo began to expand on a large scale; neighbouring houses and a convent were bought and demolished as the palazzo grew, in spite of local opposition from the neighbouring Jesuits at the Collegio Romano.

In 1767 the ceilings of the state rooms were frescoed by late-Baroque artists such as Crescenzio Onofri, Aureliano Milani, and Stefano Pozzi (Sala degli Specchi).