This study aimed to describe the protective efficacy of Moringa oleifera ethanolic extract (MOEE) against the impact of cobalt chloride (CoCl₂) exposure on the rat’s kidney. Fifty male rats were assigned to five equal groups: a control group, a MOEE-administered group (400 mg/kg body weight (bw), daily via gastric tube), a CoCl₂-intoxicated group (300 mg/L, daily in drinking water), a protective group, and a therapeutic co-administered group that received MOEE prior to or following and concurrently with CoCl₂, respectively. The antioxidant status indices (superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH)), oxidative stress markers (hydrogen peroxide (H₂O₂), 8-hydroxy-2-deoxyguanosine (8-OHdG), and malondialdehyde (MDA)), and inflammatory response markers (nitric oxide (NO), tumor necrosis factor (TNF-α), myeloperoxidase (MPO), and C-reactive protein (CRP)) were evaluated. The expression profiles of pro-inflammatory cytokines (nuclear factor-kappa B (NF-kB) and interleukin-6 (IL-6)) were also measured by real-time quantitative polymerase chain reaction (qRT-PCR). The results showed that CoCl₂ exposure was associated with significant elevations of oxidative stress and inflammatory indices with reductions in the endogenous tissue antioxidants’ concentrations. Moreover, CoCl₂ enhanced the activity of the NF-κB inflammatory-signaling pathway that plays a role in the associated inflammation of the kidney. MOEE ameliorated CoCl₂-induced renal oxidative damage and inflammatory injury with the suppression of the mRNA expression pattern of pro-inflammatory cytokine-encoding genes. MOEE is more effective when it is administered with CoCl₂ exposure as a prophylactic regimen. In conclusion, MOEE administration exhibited protective effects in counteracting CoCl₂-induced renal injury in rats.