Abstract: A novel swim bladder glue (SBG) was developed by integrating traditional E’Jiao (EJ) preparation techniques, involving prolonged simmering and concentration of intact swim bladder. The changes in its physicochemical properties and Maillard reaction products during preparation were systematically analyzed, and compared with unprocessed swim bladder collagen (SBC) and commercial EJ. An ovariectomized (OVX) osteoporosis mouse model was established to evaluate therapeutic efficacy, with femoral bone density assessed via micro-computed tomography (Micro-CT) and hepatic histopathology examined through H&E staining. Results demonstrated that SBG predominantly contained low-molecular-weight peptides (<5 kDa), with disrupted microstructure, altered secondary structure, and increased free amino acid content. In contrast, EJ and SBC exhibited dense microstructures and higher molecular weight distributions (>10 kDa). In terms of Maillard reaction, during the preparation of SBG, the contents of mid-stage Maillard reaction products (Maillard fluorescent substances, 5-hydroxymethylfurfural HMF) and late-stage product melanoidins all showed an upward trend, with a marked increase, particularly during the concentration stage. The reaction process was dominated by the mid-stage Maillard reaction. In contrast, EJ contained a high level of melanoidins and was mainly in the late stage of the Maillard reaction, while the Maillard reaction degree of SBC was low. SBG significantly increased femoral bone mineral density (BMD) in ovariectomized mice, with the high-dose SBG group (SBGH) exhibiting the most pronounced effect (206.44±17.65 mg/cm³). Moreover, SBG significantly alleviated liver inflammation, whereas neither EJ nor SBC significantly increased BMD or ameliorated liver inflammation. This study systematically analyzed the evolution of physicochemical properties and dynamic changes of Maillard reaction products during the preparation of SBG, and evaluated its bone density-improving function. The findings provide a theoretical basis for promoting the deep exploitation of swim bladder resources and elucidating the material basis of the medicinal efficacy of gelatinous traditional Chinese medicines.