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Unexplained acute kidney injury (AKI) in children owing to diethylene glycol (DEG) contamination during drug production has gained attention in recent years. This qualitative study investigated the effects of DEG exposure on the incidence of unknown AKI in children. A systematic review following the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) guidelines was proposed to search for studies using predefined search terms in the PubMed, EBSCO, and Web of Science data-bases without publication date restrictions. The inclusion criteria are observational study, case study, case report, and case series design; and having provided accurate data for DEG poisoning and AKI diagnosis in children. All authors performed the study screening, data extraction, and data synthesis processes. Consensus was reached by mutual agreement. The data synthesis was conducted according to the DEG and unexplained AKI in children by examining the statistical data using Microsoft Excel 2017 and storing the data using the cloud service of Universitas Islam Indonesia. Of the 115 included studies, 21 met the inclusion criteria, including 2 case-control studies, 1 cross-sectional study, 4 case studies, and 14 case reports. DEG-contaminated paracetamol caused unexplained AKI in children. Other drugs including cough expectorants, antihistamines, and sedatives were administered. Chemicals other than DEG, such as propylene glycol and ethylene glycol, also induce AKI owing to overprescription and unintentional exposure. A recent epidemic of unexplained AKI showed contaminated paracetamol as the poisoning agent regardless of formula.