Considering the limitations of cell therapy, in case of adequate treatment efficacy, conditioned media (CM) may be a desirable alternative to cell therapy. Hence, the present systematic review and meta-analysis aims to evaluate the efficacy of mesenchymal stem cell-derived conditioned media (MSC-CM) in movement resolution following spinal cord injury (SCI) in animal models. A comprehensive search in the databases of Medline, Scopus, Web of Science, and Embase was completed until the end of March 2021. Animal studies that evaluate the efficacy of MSC-CM on movement resolution following SCI were defined as the inclusion criteria. Lack of an SCI-untreated group, CM derived from a source other than MSC, not assessing motor function, failure to report CM administered dose, a follow-up period of less than 4 weeks, duplicates, and review articles were counted as the exclusion criteria. Final results are presented as overall standardized mean difference (SMD) with a 95% confidence interval (CI). From the 361 nonduplicate articles, data from 11 articles were entered into the present meta-analysis. The analyses showed that MSC-CM administration in SCI animal models promotes motor recovery (SMD=2.32; 95% CI: 1.55, 3.09; p<0.0001). Subgroup analysis was performed because of the noticeable heterogeneity between the studies (I2=80.97%, p<0.0001), depicting that antibiotic administration, delivery amount, delivery type, and follow-up time were the possible sources of heterogeneity. Moreover, multiple meta-regression demonstrated that in cases of delivery amount of more than 120 μL, the efficacy of MSC-CM administration in motor recovery is more than that of delivery amount of less than 120 μL (regression coefficient=3.30; 95% CI: 0.72, 5.89; p=0.019). Based on the results of the present study, it can be concluded that MSC-CM administration in SCI models improves motor recovery. The efficacy of this treatment strategy significantly increases at doses higher than 120 μL.