In 1756 the field of herbal studies was supplanted by natural history, and starting in 1759, under the direction of Giuseppe Baldassarri, the garden began to collect uncommon plants.

In 1784 the Grand Duke of Tuscany Peter Leopold began a university reform, and in a short time the garden's collection grew to contain more than a thousand new plants, many from abroad.

Today the garden is located inside Siena's city walls, covering one hillside of the valley S. Agostino.

Its central collection is arranged in systematic order within brick-bordered, rectangular flower beds, along with old specimens of exotic and local plants.

Species endemic to the garden's undeveloped areas include Alyssum bertolonii, Armeria denticulata, Centaurea aplolepa subsp.