To evaluate the effects of methanol root extract of Mahonia leschenaultii and berberine of Mahonia leschenaultii on Dalton's ascitic lymphoma in Swiss Albino mice. Methods: The methanol root extracts of Mahonia leschenaultii (200 and 400 mg/kg) were given orally, and berberines (10 and 20 mg/kg) were injected intra-peritoneally for 14 successive days in tumor bearing mice. Hematological parameters (white and red blood cells, haemoglobin level, granulocytes, and agranulocytes), lipid parameters (total cholesterol and triglycerides), serum enzymes (serum glutamate pyruvate transaminases, serum glutamate oxaloacetate transaminases, and alkaline phosphatise) and mean survival and solid tumor growth were determined and compared with untreated mice. 5-fluorouracil (20 mg/kg) was used as a reference standard drug. Results: Mahonia leschenaultii and berberine reduced the hematocrit significantly. Furthermore, Mahonia leschenaultii and berberine improved the survival of mice significantly and restored the affected hematological and lipid parameters similar to the normal levels. Conclusions: These observations show a strong anticancer effect of methanol root extract of Mahonia leschenaultii and berberine in suppressing Dalton's ascitic lymphoma cancer cell growth in a mouse model by controlling haematological, lipid, serum enzymes, and other derived parameters effectively.