Curcumin (C21H20O6) is a hydrophobic polyphenol found in turmeric. Although curcumin has been used as a natural medicine, its major limitation is related to poor absorption from the gut. Therefore, we developed a method for preparation of Curcumin Nanospheres (CN) to improve the aqueous-phase solubility of curcumin and investigate the functional role of CN in promoting feed efficiency and odor reduction in mice. CN showed inhibitory effects on actate dehydrogenase (LDH) cytotoxicity induced by ecotoxic substance toluene in gut epithelial HCT116 cells. In addition, the weights of internal organs (liver, heart, kidneys, and spleen) and the levels of serum Glutamate Oxaloacetate Transaminase (GOT), Glutamate Pyruvate Transaminase (GPT), and LDH did not show significant differences between mice administered oral CN for two weeks and compared to the control group. Interestingly, CN not only reduced hydrogen sulfide (H2S) and ammonia (NH3) levels and fecal odor, but also improved feed efficiency in mice. These results demonstrate that oral nano-delivery of anti-ecotoxicological CN is a functional system to deliver curcumin to the gut to improve feed efficiency and reduce fecal odor in mice.