eng Oriental Scientific Publishing Company Biomedical and Pharmacology Journal 0974-6242 2026-08-04 19 3 72974 article Evi Sushanty 1 Tena Djuartina 2 Ana Lucia Ekowati 3 Iskandar Rahardjo Budianto 4 Ferbian Milas Siswanto 5 Master Program in Biomedical Sciences, School of Medicine and Health Sciences, Atma Jaya Catholic University of Indonesia, Jakarta, Indonesia Department of Anatomy, School of Medicine and Health Sciences, Atma Jaya Catholic University of Indonesia, Jakarta, Indonesia Department of Medical Biology, School of Medicine and Health Sciences, Atma Jaya Catholic University of Indonesia, Jakarta, Indonesia Department of Surgery, School of Medicine and Health Sciences, Atma Jaya Catholic University of Indonesia, Jakarta, Indonesia Department of Chemistry and Biochemistry, School of Medicine and Health Sciences, Atma Jaya Catholic University of Indonesia, Jakarta, Indonesia Diabetes mellitus is associated with sustained hyperglycemia, oxidative stress, impaired antioxidant defense, and pancreatic tissue injury. Medical ozone has been proposed as an adjunctive intervention because controlled low-dose ozone exposure may induce oxidative preconditioning and stimulate endogenous antioxidant responses. However, the available evidence remains scattered and is mainly derived from animal experiments.This systematic review and meta-analysis aimed to summarize the effects of medical ozone on glucose regulation, oxidative-stress biomarkers, and pancreatic histological changes in preclinical models of diabetes.PubMed, EBSCOhost, Google Scholar, and ProQuest were searched from database inception to September 2025. The review followed PRISMA 2020 guidance. Original preclinical studies using diabetic animal models treated with medical ozone were eligible when they reported metabolic, oxidative-stress, or pancreatic histological outcomes. Study screening, data extraction, and risk-of-bias assessment using the SYRCLE tool were performed by two reviewers. Quantitative pooling was conducted in RevMan 5.4 using standardized mean differences (SMDs) with 95% confidence intervals (CIs).Four studies met the inclusion criteria. Pooled analysis showed lower post-treatment blood glucose after ozone administration (SMD = -5.55; 95% CI: -6.67 to -4.43). Ozone therapy was also associated with reduced malondialdehyde levels (SMD = -5.09; 95% CI: -9.30 to -0.87) and higher glutathione concentrations (SMD = 3.87; 95% CI: 0.83 to 6.90), whereas findings for superoxide dismutase were inconsistent. Histological findings generally indicated better preservation of pancreatic islet architecture and less tissue injury in ozone-treated animals. In preclinical diabetic models, medical ozone may improve glycemic status, reduce selected oxidative-stress markers, and preserve pancreatic morphology. These findings should be interpreted cautiously because the evidence is limited to a small number of heterogeneous animal studies. Further rigorously designed preclinical studies are required to define optimal protocols, clarify mechanisms, and determine whether clinical translation is appropriate. https://biomedpharmajournal.org/vol19no3/medical-ozone-as-an-adjunct-for-glucose-regulation-and-oxidative-injury-modulation-a-systematic-review-and-meta-analysis-of-preclinical-studies/ Diabetes mellitus Medical ozone Oxidative stress Pancreatic histology Systematic review