Background <p>Nephrotoxicity, oxidative stress, and inflammation have all been connected to pesticide and xenobiotic exposure. Here, we evaluate the protective potential of <i>Xylopia</i> <i>aethiopica</i> stem-bark ethanol extract (XASEE) on glyphosate-induced nephrotoxicity in Wistar rats.</p> Method <p>The plant stem-bark was subjected to cold maceration in 50% ethanol and the obtained extract was lyophilized. The phytochemicals in the extract were analysed while Lorke’s method was used for its acute toxicity study. In a 7&#xa0;day study, rats (36) were grouped into six (n = 6 each) and treated as follows; control, glyphosate (150&#xa0;mg/kg b.wt), glyphosate + XASEE (1/10 th of extract -LD₅₀), glyphosate + vitamin C (250&#xa0;mg/kg), XASEE and vitamin C only.</p> Results <p>Phytochemical analysis indicated saponins, tannins, phenolics, flavonoids, glycosides, steroids, and alkaloids. Phenolics have the highest level (492.84 ± 0.01&#xa0;mg/100&#xa0;g) while glycosides were least (7.01 ± 0.02&#xa0;mg/100&#xa0;g) in XASEE. The estimated LD₅₀ was 1264.91&#xa0;mg/kg b.wt. Oral exposure of rats to glyphosate significantly increased the concentrations of creatinine, urea, and uric acid in the serum and the level of MDA, NO, creatinine, IL-6 and TNF-α in kidney homogenate. Also, there was a decrease in antioxidant enzymes activities of GPX, SOD, GSH, and CAT with no significant alteration in the concentration of serum electrolytes (K⁺, Na⁺, Cl⁻, and HCO₃⁻ ions) in glyphosate group compared to the control. Meanwhile, co-administration of XASEE after 2&#xa0;h of administration of glyphosate ameliorate this incidence of nephrotoxicity, lipid peroxidation and inflammation.</p> Conclusion <p>The result shows XASEE confers protective attributes against glyphosate-induced nephrotoxicity, oxidative stress, and inflammation.</p>