Overlooking Piazza della Meridiana, the palace was the backdrop to Strada Nuova for more than a century, preventing, with Gerolamo Grimaldi's Palace, a building directly opposite, the natural continuation towards the west, which did not occur until the 1770s (1786) with the opening of Strada Nuovissima (today Via Cairoli).

The building was erected between 1626 and 1628 on the commission of Giovanni Battista Brignole, who had it built by Bartolomeo Bianco.

The magnificence that the Brignole family wanted for their residence during the 17th and 18th centuries is still witnessed by the frescoes that illusionistically break through the vaults of the rooms on the piano nobile, where Gregorio and Lorenzo De Ferrari frescoed stories of Flora, Prometheus giving life to the statue, Aurora and Diana in search of Endymion.

The marble busts in the main hall on the piano nobile are also of great value.