Purpose The primary objective of this study was to conduct a comparative analysis of the anti-inflammatory activity between Etoricoxib (ETO) and Matcha green tea (MG) in the context of acute kidney injury (AKI) induced by ionizing gamma radiation (IR) in female rats. Furthermore, the potential impact of whole body IR exposure on the intestinal system and serum estradiol levels was investigated. Additionally, it was acknowledged that the ETO and MG treatments might have exerted favorable effects on the intestinal and hormonal responses. Materials and Methods Six groups of rats were assigned to different treatments: control, ETO, MG, irradiation (IRR), ETO + IRR, and MG + IRR. The evaluation included measuring the total phenolic and flavonoid contents of ETO and MG, as well as assessing their antioxidant activity, radical scavenging capacity, reducing power, and total antioxidant capacity. Kidney function was assessed through serum creatinine and urea levels. Oxidative stress markers, including superoxide dismutase, glutathione, malondialdehyde, and catalase, were measured to evaluate the antioxidant effects of ETO and MG. The anti-inflammatory potential of the treatments was evaluated by measuring STAT-3 and interleukins (IL-6, IL-23, and IL-17) using an ELISA assay. Prostaglandin E2 receptor (PGE-2) mRNA expression, histopathological examination, and immunohistochemistry for NF-κB inhibitors were performed to investigate the underlying mechanisms in kidney tissue homogenates. Histopathological changes and DNA fragmentation in the intestinal tissues were determined, and the characterization of Matcha green tea was performed using liquid chromatography-mass spectrometry (LC-MS). This allowed for the identification and quantification of various compounds present in Matcha green tea. Furthermore, the study assessed the effect of IR and treatments on estrogen levels in female rats. Results Data showed that both ETO and MG had the potential to mitigate the adverse effects of AKI induced by IR. Notably, MG exhibited greater efficacy in attenuating oxidative stress and inflammation associated with renal injury. These findings revealed and compared the effects of ETO and MG in alleviating AKI caused by IR. MG demonstrated greater anti-inflammatory and antioxidant properties, highlighting its potential as a natural therapeutic agent. Conclusions These results contribute to the growing evidence supporting the use of MG in managing IR-induced renal complications. Future studies should focus on elucidating the molecular mechanisms and optimizing the application of MG in clinical settings.