To meet the ever-increasing energy demands, oil and gas exploration is progressively extending into deep formations with high temperatures and high salinity, presenting new challenges for the performance improvement of fluid-loss additives in drilling fluids. From the perspective of controllable polymer structure design, this review systematically elucidates the intrinsic relationship and development trends between polymer molecular structures and their fluid-loss control. First, the adverse effects of high temperature and high salinity environments on bentonite and polymers are elucidated, revealing the fundamental causes of uncontrolled filtrate loss under extreme conditions. Subsequently, focusing on four major research trends—optimization of polymerization methods, design of polymer monomers, construction of ultra-stable structures, and controlled incorporation of inorganic materials—the fundamental principles for precise molecular construction and performance enhancement are thoroughly discussed. In addition, the environmental and economic impacts of these fluid-loss additives are discussed in detail, including monomer selection, synthesis methods, and subsequent treatment processes. Finally, this review summarizes the key challenges associated with high-temperature and high-salinity conditions and outlines specific future research directions for developing highly efficient fluid-loss reducers. In summary, this review provides a comprehensive overview of recent advances in synthetic polymer-based fluid-loss additives and offers guidance for developing multidimensional, highly efficient fluid-loss additives.