Abstract Background and Aims Complications associated with Chronic Kidney Disease (CKD), such as disease progression and anemia, are closely linked to heightened inflammation mediated by the innate immune response. This inflammation can be mitigated through the use of anti-inflammatory agents. 6,6′-dihydroxythiobinupharidine (DTBN), an active compound derived from the aquatic plant Nuphar lutea, demonstrates notable anti-inflammatory properties, primarily by inhibiting NF-κB and LPS-induced cytokine activation. DTBN has shown efficacy in priming neutrophils, enhancing phagocytosis, regulating reactive oxygen species (ROS) production, and modulating NET formation. This study aimed to assess the impact of DTBN on CKD in mice. Method Male C57BL/6J mice, aged 8 weeks, were subjected to an adenine diet known to induce CKD through crystal deposition and tubulointerstitial inflammation. Both control and CKD-induced mice received intraperitoneal injections of DTBN (25 μg QOD) or saline and were euthanized after 8 weeks for evaluation. Results CKD mice treated with DTBN exhibited a significant decrease in serum urea and creatinine levels compared to untreated CKD mice (reduction by 1.4-fold and 1.3-fold, respectively). Histological analysis of kidney tissues revealed a notable reduction in F4/80 positive macrophage infiltration (3.4-fold decrease) and damaged renal areas (three-fold decrease), along with diminished kidney TGF-β levels in DTBN-treated CKD mice. Moreover, the p65 subunit of NF-κB showed a three-fold reduction in CKD mice treated with DTBN compared to untreated CKD mice. Indices of kidney inflammation (IL-1β, IL-6, and P-STAT3) were notably decreased in CKD mice treated with DTBN (reduction by 1.4-fold, 1.6-fold, and 2.9-fold, respectively) compared to untreated CKD mice. Notably, DTBN treatment in control mice did not induce apparent tissue damage; however, it led to reduced weight gain and mild hypoalbuminemia without proteinuria. Conclusion DTBN demonstrated significant improvements in renal function and inflammation indices in CKD mice. Hence, DTBN and substances similar to DTBN could be considered as supplementary treatments for CKD patients.