The combined extract of Spermacoce radiata and Hypselodelphys poggeana leaves has been shown to be a potent therapeutic agent against benign prostatic hyperplasia which is used extensively for BPH and other diseases by local traditional medicine practitioners without any evaluation of its toxicity effects on liver and other vital organs in the body.  The study evaluated the hepatoprotective effects of a combined extract of S. radiata and H. poggeana (CEESH) on rats with prostate enlargement (BPH). We had five groups of rats (n = 6), with groups 1 and 2 being the normal and BPH controls, respectively. Groups 3, 4 and 5 were the BPH rats administered Finasteride, 300 and 600 mg/kg CEESH, respectively. Prostate enlargement was induced in the rat by the subcutaneous administration of testosterone injection (5 mg/kg/day for 28 days), while Finasteride and CEESH were respectively administered to the rats orally as therapeutic agents. Prostate enlargement in the rats elevated AST, ALT, and ALP activities in BPH control coupled with a significant rise in the serum bilirubin levels compared to the normal control. The total protein and its constituents (including albumin and globulin) declined significantly in the BPH control compared to the normal control. Administration of CEESH to the prostate enlarged rats lowered AST, ALT, and ALP activities in groups 4–5 rats significantly (P<0.05) compared to BPH control. Besides, the CEESH treated had elevated total protein (including albumin and globulin) levels compared to the BPH control. The high bilirubin levels in the BPH control were significantly diminished in the rats treated with CEESH. No alterations in the liver micrographs of the BPH control and CEESH administered rats were observed. These findings showed that CEESH confers hepatoprotection in BPH induced rats and could be used to manage BPH and other hepatic disorders.