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Abstract Mineral scaling represents a major constraint that limits the efficiency of membrane desalination, which is becoming increasingly important for achieving sustainable water supplies in the context of a changing climate. Different mineral scales can be formed via distinct mechanisms that lead to a significant variation of scaling behaviors and mitigation strategies. In this article, we present a comprehensive review that thoroughly compares gypsum scaling and silica scaling, which are two common scaling types formed via crystallization and polymerization respectively, in membrane desalination. We show that the differences between scale formation mechanisms greatly affect the thermodynamics, kinetics, and mineral morphology of gypsum scaling and silica scaling. Then we review the literatures on the distinct behaviors of gypsum scaling and silica scaling during various membrane desalination processes, examining their varied damaging effects on desalination efficiency. We further scrutinize the different interactions of gypsum and silica with organic foulants, which result in contrasting consequences of combined scaling and fouling. In addition, the distinctive mitigation strategies tailored to controlling gypsum scaling and silica scaling, including scaling-resistant membrane materials, antiscalants, and pretreatment, are discussed. We conclude this article with the research needs of attaining a better understanding of different mineral scaling types, aiming to inspire researchers to take scale formation mechanism into consideration when developing more effective approaches of scaling control in membrane desalination.