Background: Current treatment for patients with autism spectrum disorder (ASD) is for specific symptoms or comorbidities, but patients remain affected, suggesting a need for more effective treatment. Mesenchymal stem cell (MSC) therapy could benefit patients with ASD due to its genetic and immunological etiology. MSC therapy has significantly reduced disease severity in patients with neurological disorders. We aim to identify evidence on safety and efficacy of MSC therapies for treatment of children with ASD, without comorbidities.Methods: Systematic literature review in five indexed databases, three clinical trial registries, and gray literature. Search strategies were run on April 14 of 2022 and May 05 of 2023; were composed of free terms and exploited controlled vocabulary. Performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. We included controlled clinical trials with or without randomization; studies with comparator arm with MSC at different doses, placebo, or standard therapy, and published in English, Spanish, French, or Portuguese. We excluded studies with other experimental therapies. References were screened and selected by two independent reviewers. Bias evaluation and qualitative synthesis were conducted. PROSPERO register: CRD42022329255Findings: 601 studies were obtained. After applying selection criteria and quality evaluation, two studies (n=44; 81·8% male) were included, which evaluated the change in Clinical Global Impression (CGI) scale after MSC therapy. One study presented qualitative results, reporting a maximum (1/12), minimal (8/12), and no change (3/12) on patients; the other study reported no statistically significant differences for total scale’s score, only for disease severity component in the intervention group (mean -1·35 standard deviation (SD) 0·49) compared to the control group (mean -0·66 SD 0·68) (p=0·004). No serious adverse events were reported.Interpretation: Evidence suggests that MSC therapy in ASD children without comorbidities is safe and possibly useful in clinical practice. However, more clinical trials of higher quality are required.Funding: Bioxcellerator.Declaration of Interest: The authors work for BioXcellerator, an institution that conducts research in advanced therapies with Mesenchymal Stem Cells derived from Umbilical Cord Wharton Jelly. However, the authors declare independence as the research development group.