The history of Esanatoglia during Middle Ages is easier to reconstruct, with the origins of the Church dedicated to Santa Anatolia.
According to Feliciangeli, being brought up “under the discovered grave of the martyr", religious organisms where multiplying across the peninsola with a baptismal and centralisation function for the Christianity faith, especially for the rural population, dispersed in an extense territory.
Additionally, there is the first famous document with references to Santa Anatolia dating back from 1015, regarding the foundation of the Monastery of Sancti Angeli infra hostia (Sant'Angelo), annexed to the pre-existent church, according to the will of Conte Atto and his wife Berta.
A second written memory in 1040 textually mentions the Castrum Sancte Anatholiae. The Church of the Pieve is mentioned in a decree of 1180 that establishes the donation, from Conte Malcavalca di Albertino (Lord of Fiuminata, of the villa of the Palace and, presumably, of the Castle of Santa Anatolia), of half of his lands of Ecclesia Baptismatis to the Monastery of Sant'Angelo.
The Monastery of Sant'Angelo had become, at that time, the most important religious settlement in the entire valley, so much that made Pope Innocenzo III (1198) confirm its domain over approximately 40 churches in the Diocese of Nocera Umbra, Camerino and Osimo.
The feudal Malcavalca was sucedeed by Ottoni di Matelica (1211) that ruled three years later. The Guelfs of Camerino, along with the powerful Da Varano family, ruled for the next three centuries with an easy acceptance by the citizens of Santa Anatolia, who were certain to enjoy greater freedom under a goverment geographically more distant. Santa Anatolia would not see invasions or wars for a long period.
:: Eremo di San Cataldo
Along with the evolution of the civil powers there was also a consistent development of the religious one: rising and proliferating beyond the Abbadia di Sant'Angelo and the rural villa, the Monastery of Fonte Bono (on the slopes of the Monte Consegno), and later within the walls, the one of Sant'Agostino and the Convent of Santa Maria Maddalena.
Additionally, there were the Hermits churches which, until the end of the XVI century, at least three can be identified:
:: San Cataldo
under the rules of the Monastery of Fonte Bono
:: San Pietro
placed near the source of the Esino river
:: San Lorenzo
which arises from the slopes of Monte Gemmo
Exactly for these peculiarities and for the strategic position of the Castle, the Curia Romana, already in 1240 and later in 1283 and 1356, had demanded the ownership, which they never desired to obtain by force, in order to secure the loyalty of Camerino against the Emperor Federico II, whose military army was invading Marche with the support from the Ghibellini.
The Varano clan mantained the power until 1502 when Pope Alessandro VI (Borgia) overthrough them definitely. Only for a brief moment, around 1443, as a result of a siege, Francesco Sforza, assisted by the people of Matelica, is able to conquer and takeover the Cittadella and land of Santa Anatolia; the Monastery of Sant'Angelo and its famous library were not immune and became destroyed in the aftermatch.