Doxorubicin-induced organ toxicities, through inflammation and oxidative stress, reduce its widespread use in the treatment of cancer. Thus, there is need for the development of less toxic and more effective plant-derived drugs and spice supplements to mitigate inflammation and oxidative stress induced by doxorubicin. The present study investigated the phyto-chemical profile and ameliorative potential of Allium vineale bulb methanol extract (AVBME) on doxorubicin-induced oxidative stress and inflammation in Sprague Dawley rats. Forty-nine (49) male Sprague Dawley rats were randomly stratified into 7 groups with 7 rats per group. Groups A and B received distilled water for 7 days. Groups C, D, and E were pretreated for 7 days with 200 mg/kg silymarin, 500 mg/kg, and 1000 mg/kg AVBME, respectively followed by intraperitoneal injection of 20 mg/kg doxorubicin (DOX) to groups B, C, D, and E on the 8th day. Groups F and G were orally administered 500 mg/kg and 1000 mg/kg AVBME respectively for 7 days with an intraperitoneal injection of distilled water on the 8th day. The AVBME GC–MS analysis revealed the presence of 21 phyto-compounds, rich in flavonoids and LD50 ˃ 2000 mg/kg. AVBME exhibited a very strong inhibitory activity against DPPH, ABTS+, OH., NO, and H2O2 with IC50 values of 0.09, 0.01, 0.036, 2.09, and 3.57 mg/ml respectively. Pre-treatment with AVBME and Silymarin for 7 days increased the PCV, RBC and lymphocytes with the highest WBC count recorded in DOX-administered rats compared to the healthy control. Also, pre-treatment with AVBME for 7 days significantly (p < 0.05) decreased the levels of AST, ALT and ALP in the serum while improving the levels of urea and electrolytes to near basal level in the serum and kidneys. However, doxorubicin administered on the 8th day significantly (p < 0.05) reduced the levels of GSH and antioxidant enzymes in the serum, liver, heart and kidneys while the levels of TNF-α and C-reactive protein increased. Interestingly, pre-treatment with AVBME for 7 days elevated IL-10 and reversed all the alterations induced by doxorubicin toxicity. Also, doxorubicin induced degenerative hepatic, nephrotic and cardiac biochemical and histological changes, while remarkable reversal of these pathological features was observed in groups pretreated with AVBME. AVBME protects the liver, heart and kidneys of Sprague Dawley rats through antioxidative and anti-inflammatory effects.