The therapeutic effects of bone marrow mesenchymal stem cells (BMSCs) and their conditioned media have been well-documented. This study focused on the effects of BMSC-conditioned medium (BMSCcm) on spinal cord injury (SCI). To study the effects of BMSCcm on rat motor function, inflammatory response, and M1/M2 macrophage/microglial polarization, SCI model rats were treated with BMSCcm and vectors for overexpression of galectin-3 (Gal-3) or NLR family pyrin domain containing 3 (NLRP3). Treatment with BMSCcm reduced the expression of Gal-3 and NLRP3, alleviated the inflammatory response, suppressed M1 microglia/macrophage polarization, and triggered M2 microglia/macrophage polarization in SCI model rats. Meanwhile, overexpression of Gal-3 or NLRP3 counteracted the suppressive effect of BMSCcm on SCI. Moreover, during BMSCcm treatment, overexpression of Gal-3 promoted the expression of NLRP3, whereas overexpression of NLRP3 had no significant effect on the expression of Gal-3. Additionally, the effects of BMSCcm on macrophage/microglial polarization and the underlying molecular mechanisms were observed in vitro. This study demonstrated that BMSCcm alleviates SCI by suppressing the expression of Gal-3 and NLRP3.