In an area adjacent to the Romanesque Pieve, in the 1980s, the remains of a large Roman villa were found, which, after the immediate constraint decided by the Ministero pe i beni culturali e abientali, is waiting to be brought to light.

The oldest document where Medole is mentioned is a deed dated May 31, 841, by which the bishop of Brescia Ramperto donated to the Benedictine Monks, whom he had brought from France, some properties in the countryside, including the House of San Vito.

Around the second half of the 15th century the municipality, for reasons not known, probably due to a severe famine in the Brescian valleys, was subject to an unexpected and massive immigration that, in a short time, led to a significant increase in the population of Medolese.

During the War of Succession of Mantua and Monferrato in 1629, the territory of Medole and neighboring municipalities suffered raids by Albrecht von Wallenstein's German and Polish mercenaries, led by the Count of Collalto, who perpetrated theft and killings and brought a severe plague epidemic.

The 20th century began under good auspices because of economic improvements due to the activities of the Cooperativa Agricola Italiana, which in 1901 established an important rural cooperative enterprise in Medole, partly clearing agrarian labor from the control of landowners and encouraging the humbler classes of the population to study.