This study was designed to evaluate the protective effect of Calocybe indica extract (CLE) on testosterone propionate (TP)-induced hematological changes and oxidative stress in rats. The rats were grouped into six equal groups of ten rats each as follows:(a) control, (b) TP 3 mg/kg only, (c) 3mg/kg TP+ 5 mg/kg finasteride, (d) 3 mg/kg TP+250 mg/kg CLE, (e) 3 mg/kg TP+ 500 mg/kg CLE and (f) 3 mg/kg TP+1000 mg/kg CLE. The rats were administered TP subcutaneously for 28 days to induce benign prostatic hyperplasia (BPH) and simultaneously administered three graded doses of CLE, and finasteride as the standard drug. Hematological parameters, lipid peroxidation, antioxidant enzyme activities and histopathological examination of the prostate were assessed. BPH induction showed higher red blood cells (RBCs) count, haemoglobin (Hb) concentration, packed cell volume (PCV), serum prostate specific antigen (PSA), malondialdehyde (MDA) and lower white blood cell (WBC) count, lymphocyte count as well as lower catalase (CAT) and superoxide dismutase (SOD) activities. The simultaneous oral administration of CLE with testosterone injection did not significantly lower RBC count, Hb concentration and PCV but significantly lowered serum PSA and MDA. There was also a significantly higher WBC count, lymphocyte count, CAT and SOD activities. The results from this study suggest that dietary consumption of Calocybe indica, a mushroom with high antioxidant activity ameliorated BPH induced oxidative tissue damage and hematological alterations.