The walls of the Oratorio of San Giovanni Battista in Urbino are decorated with outstanding mural paintings dating back to the 15th century. Due to degradation processes that have occurred in the past years, such paintings require a conservative restoration project. In order to evaluate reasons of the decay, some scientific studies have been performed. They consist of macroscopic observations and chemical (EDS), morphological (SEM) and mineralogical (XRD) analyses of samples both from the original preparatory layers under the painted layers and from the restored plasters at the surbase of the wall. In addition, environmental studies have been performed to verify microclimatic conditions of the church in which the mural paintings are located. Finally, a conservative restoration project was proposed.