This work aims at studying the impact of silane-based coatings, generated by atmospheric pressure plasma spraying (APPS) of a liquid precursor (hexamethydisiloxane – HMDSO), on dairy antifouling and antibacterial properties of food-grade 316L stainless steel. The influence of the manufacturing parameters (precursor flow rate, nozzle-to-substrate distance and scanning speed) on the coatings properties was investigated using a wide range of characterization techniques (drop shape analysis, X-Ray Mappings, Scanning Electron Microscopy, Fourier-Transformed Infrared Spectroscopy, Atomic Force Microscopy). Coating’s roughness in particular was shown to strongly increase when precursor flow rate increases. A pilot pasteurizer, fed with a model foulant solution (whey protein and calcium), allowed performing two consecutive industrial-like isothermal dairy fouling tests, revealing the promising anti-fouling properties of the HMDSO-coated steel. A fouling reduction of up to 90% compared to bare stainless steel was achieved after first cycle for all samples. The second fouling run allowed to select the best-performing sample, which kept the same antifouling properties as in the first test. Its mechanism of action was investigated, which revealed that a nanostructured, Si-O-Si rich surface was efficient to prevent isothermal dairy fouling. The adhesion of the pathogenic bacterium Staphylococcus aureus also proved to be impacted by this plasma coating, with a significant decrease of adhered cells (−30% compared to native stainless steel).