Dimethyl sulfoxide (DMSO) has been used for medical treatment and as a pharmacological agent in humans since the 1960s. Today, DMSO is used mostly for cryopreservation of stem cells, treatment of interstitial cystitis, and as a penetrating vehicle for various drugs. Many adverse reactions have been described in relation to the use of DMSO, but to our knowledge, no overview of the existing literature has been made. Our aim was to conduct a systematic review describing the adverse reactions observed in humans in relation to the use of DMSO. This systematic review was reported according to the PRISMA-harms (Preferred Reporting Items for Systematic reviews and Meta-Analysis) guidelines. The primary outcome was any adverse reactions occurring in humans in relation to the use of DMSO. We included all original studies that reported adverse events due to the administration of DMSO, and that had a population of five or more. We included a total of 109 studies. Gastrointestinal and skin reactions were the commonest reported adverse reactions to DMSO. Most reactions were transient without need for intervention. A relationship between the dose of DMSO given and the occurrence of adverse reactions was seen. DMSO may cause a variety of adverse reactions that are mostly transient and mild. The dose of DMSO plays an important role in the occurrence of adverse reactions. DMSO seems to be safe to use in small doses. PROSPERO CRD42018096117.