The use of the quartz crystal microbalance (QCM) has gained prominence in detecting nanoscale mass changes due to the high sensitivity of piezoelectric quartz crystals. Originally used in communication circuits, these crystals are now widely employed as acoustic sensors, allowing real-time detection of molecular interactions on surfaces, such as biological membranes. Since Sauerbrey’s demonstration in 1959, which established the direct proportionality between the resonant frequency change and mass alteration, QCM has become an essential tool for investigating cell adhesion interactions and pathogen detection. The significance of nanoparticles (NPs), especially gold nanoparticles, in scientific applications has grown due to their unique properties and large specific surface area. QCM has proven effective in characterizing nanomaterials and their interactions with artificial membranes, which is particularly valuable in the food science sector. This technique facilitates the detection of contaminants, monitoring of food freshness, and study of molecular interactions relevant to food quality and safety. This chapter presents an experimental protocol to determine the kinetic and thermodynamic parameters of interactions between gold nanoparticles, functionalized with HS-PEG6000-OCH3, and an artificially constructed membrane on QCM. An aqueous dispersion of the nanoparticles is injected into the QCM, allowing real-time monitoring of mass changes and molecular interactions on the membrane surface. The experimental protocol includes cleaning the quartz crystal, forming the supported lipid bilayer (s-BLM), preparing nanoparticle dispersions, instrument calibration, and measuring nanoparticle-membrane interactions. Obtained data are analyzed to determine binding constants and kinetic parameters using mathematical models and computational codes developed in Octave. This work significantly advances the study of interactions in nanostructured systems and the development of efficient and sensitive biosensors applicable in various fields, including food science. In food science, QCM can be used to detect contaminants such as pathogens and pesticides, monitor the freshness and quality of food products, and study interactions between various food components at the molecular level. This experimental protocol contributes to developing new methods for ensuring food safety and quality, highlighting the critical role of QCM in advancing food science research.