Adriamycin (ADR), though, a drug of choice in cancer therapy, its use is associated with acute and chronic complications, which are capable of exacerbating the conditions of the patients. Thus, efforts are being directed at evaluating several compounds, antioxidants and natural products that are capable of ameliorating these complications whilst still retaining the potency and efficacy of Adriamycin as an anti cancer agent. The modulatory and ameliorative effects of methanol guava leaf extract (MGLE) (Psidium guajava Linn) against Adriamycin/Doxorubicin toxicity was evaluated in Wistar rats. Thirty Male rats were divided into six groups A – F of five rats each, Group A fed normal saline, B- single acute dose of ADR, C- 500mg/kg guava extract alone, D to F -ADR in combination with 125, 250 and 500mg/kg body weight of guava leaf extracts,(MGLE) respectively for seven days after which blood samples were collected from all the animals. Liver and kidney damage markers were assessed in serum, liver histopathology, and micronucleated polychromatic erythrocytes (mPCEs) from bone marrow were assessed, and data represented as mean ± SE. Adriamycin resulted in considerable liver and kidney damage as seen in the form of elevated liver enzymes, total protein as well as urea and creatinine levels. It also resulted in significant (P<0.05) increases in the total triglyceride and cholesterol levels. The use of the extract alone on the other hand showed hepatoprotective and nephroprotective properties of guava leaf extract in that the above parameters were significantly lower than those of the untreated control. Hepatic histopathology indicated no visible lesion in the control group, necrotic hepatocytes observed in ADR, no visible lesion seen in the MGLE treated group and mild mononuclear cellular infiltration in ADR +MGLE treated groups. ADR induced significant mPCEs formation in rat bone marrow (P < 0.05), a dose dependent decrease (P < 0.05) in mPCEs in ADR + MGLE rats compared with ADR was observed. The MGLE exhibited hepatoprotective and anticlastogenic potentials. Our findings suggest that MGLE may mitigate the effect of ADR-induced toxicities.