Istia d'Ombrone (Italian: [ˈistja domˈbroːne]) is a small town in southern Tuscany, Italy, a frazione of the comune of Grosseto.

It was inhabited also during the Roman era, as testified by some construction materials reused in later periods to build the walls of Istia.

However the centre of Istia arose as a settlement fortified along the Valley of Ombrone and from 862 was owned by the bishops of Roselle, which had feudal rights with the title of counts and so here they established a residence.

In the course of the 14th century it passed under the control of Siena, enduring a very serious demographic decline between 1331 and 1353, also because of the diffusion of the Yersinia pestis which occurred right at the end of that period.

In the 15th century Istia had become a feud of the Piccolomini family, even though it continued to maintain the status of free Comune and having a high degree of autonomy within the Republic of Siena.