<p>Inorganic scaling, governed by complex organic–inorganic interactions, presents a pervasive challenge in aqueous environments with broad implications for engineering systems. Using reverse-osmosis (RO) desalination as a model platform, we investigate how mixed organic foulants influence inorganic gypsum scaling at membrane–water interfaces. Representative proteins, humic substances, and polysaccharides are employed as model foulants to reveal their roles in modulating gypsum crystallization behavior. By integrating advanced in situ, time-resolved synchrotron X-ray scattering within the concentration polarization layer—a region typically inaccessible to conventional characterization techniques—with modelling, spectroscopic, and imaging analyses, we track the evolution of gypsum scaling from nanoscale precursors to mature crystals. Our findings reveal that different classes of organic foulants regulate gypsum crystallization through distinct mechanisms, ranging from inhibiting precursor aggregation in the bulk solution to altering interfacial physicochemical properties that govern the kinetics of heterogeneous nucleation and growth. These findings provide molecular-level insights into the coupled dynamics of organic fouling and inorganic scaling, advancing mechanistic understanding of crystallization at functional interfaces. Such insights offer guidance for the rational design of anti-scaling strategies in engineering systems.</p>