Polyhedral oligomeric silsesquioxanes (POSSs) can be utilized to prepare nanocomposites to improve their physical and mechanical properties significantly by physical interaction and chemical cross-linking. The purpose of this work is to prepare a kind of water-dispersive POSS containing multiple epoxy groups and then use it to prepare gelatin/POSS nanocomposites to enhance their thermal and mechanical properties. Accordingly, 3-glycidyloxypropyl-POSS (G-POSS) was synthesized by a complete hydrolysis and condensation method. Then, G-POSS was modified with polyetheramine to obtain a derivative material of POSS, denoted as P-G-POSS, which possess better water dispersion and flexibility. Importantly, the chemical structure of both G-POSS and P-G-POSS was confirmed by FT-IR, NMR, XPS and EDS analyses. Subsequently, POSS/gelatin nanocomposites were prepared in accordance with 1:1, 2:1 and 3:1 of epoxy/amino mole ratios in alkaline aqueous medium. The microscope porous structure, thermal stability, mechanical properties, along with water absorption of the composites containing various contents of P-G-POSS, were emphatically studied and discussed. The results indicated that composites possessed the maximum denaturation temperature up to 80.1 degrees C, as well as the increased initial decomposition temperature and residual mass at 700 degrees C, and particularly improved mechanical properties after incorporation of P-G-POSS into gelatin matrix. The reason is likely that the cross-linking reaction of epoxy groups in P-G-POSS with amino groups in gelatin macromolecules, along with hydrogen bonding, played an important role in the as-prepared gelatin/POSS composites. This study would be helpful to promote the application of POSSs in bone tissue regeneration and leather cleaner production.