Fast acting topical hemostatic agents play a key role in hemorrhage control. Retarding fibrinolysis is also critical in improving coagulation, thereby expanding chances of survival. The purpose of the present work was to investigate the physical properties, loading capacity and hemostatic efficacy of newly developed nanoclay microsphere frameworks (NMFs) loaded with tranexamic acid (TA), as antifibrinolytic agent. Nanoclay compositions were prepared with increasing levels of TA. Results showed that TA was successfully incorporated into the nanoclay structure and released when solvated with ethanol. Both doped and undoped NMFs significantly decreased activated partial thromboplastin time and increased clot stiffness, which was attributed to significantly thinner fibrin fibers and a denser clot structure.