Biocleaning technology is based on the use of safe environmental microorganisms for green cultural heritage (CH) restoration. Compared with traditional cleaning products, this biological technique is very specific, effective, and nontoxic. This innovative biotechnological application has been used for recovering diverse monuments and artworks. Most CH in situ surfaces that are treated with microorganisms are small areas; however, some important pathologies, such as salt contamination, can affect high dimension artistic surfaces. The purpose of this study is to analyze and overcome the problems and limitations of scaling up the bio-desalination protocol for in situ applications. Three water-based gel delivery systems and three heating systems were tested in situ and evaluated in terms of performance difficulty, efficacy, and costs. The tests were carried out on the salt contaminated granite pavement of Cristo Chapel of Sta Ma de Conxo in Santiago de Compostela (Spain). Ground agar 2% and a heating electric mat were selected as the best performing systems. The implemented protocol was applied for the bio-desalination of the 233 m2 Chapel pavement. Conductivity, nitrate–nitrite measurements, biological monitoring, and digital image analysis were performed to determine the efficacy of the treatment. This research allowed for the development of an innovative and optimized in situ, high dimension bio-desalination application protocol transferable to other large scale, in situ biocleaning strategies.