Oxidative stress can play an important role in the autoxidation of glucose, glycation of proteins and activation of polyol metabolism, and the development of various complications in diabetes. This study investigated the protective effect of Paliurus spina-christi (PSC) fruit against diabetes-induced pathologies such as inflammation caused by oxidative stress and its phytochemical content. The bioactive compounds of Paliurus spina-christi fruit extract (PSC-FE) prepared by the infusion method were determined by LC-MS/MS analysis, and the metal reduction and radical removal activity were determined in vitro by DPPH, ABTS, FRAP and CUPRAC methods. The effect of PSC-FE on catalase and superoxide dismutase enzymes and lipid peroxidation in streptozotocin-induced diabetic rat tissues was determined in vivo. For determining in vivo antioxidant activity, the study was carried out on 30 Wistar albino male rats that were distributed into 3 research and 2 control groups. As a result of LC-MS/MS analysis, malic acid (28,424.18 +/- 3.21 mu g/g PSC-FE) and rutin (23,459.68 +/- 3.73 mu g/g PSC-FE) are the highest among the 22 phenolic compounds. The PSC fruit water extracts were determined to have a more powerful antioxidant activity than standard antioxidants. In those groups that received PSC-FE, catalase and superoxide dismutase enzyme levels that decreased in patient group were found to have a statistically meaningful increase in treatment groups (P < 0.01). Although malondialdehyde amount, the last product of lipid peroxidation, was observed to have a statistically meaningful increase in patient group when compared with control group, this increase was decreased in all treatment groups in a statistically meaningful manner (P < 0.01). The PSC was seen to be more successful, when compared with standard antioxidants. The PSC-FE was found to have a rich phenolic diversity. It can be said that the PSC may have a significant therapeutic effect on diabetes caused by oxidative stress due to its biological activities and content.