This study evaluated the fertility-enhancing activity and safety of aqueous extract of Chasmanthera dependens root (AECDR) in male rats. In the fertility study, twenty, sodium arsenite (10 mg/kg) body weight (BW)-treated male rats (171.02 ± 3.36 g), assigned into four groups (I–IV), received 1 ml of distilled water (DW), 25, 50 and 100 mg/kg BW of AECDR for 60 days, whereas the control received DW. After 7 days of pairing with female rats (153.67 ± 2.24 g), spermatogenic, fertility, testicular function indices and enzymatic antioxidant activities were evaluated. The animal groupings in the toxicity study were similar to the fertility study except no administration of sodium arsenite. Sodium arsenite treatment-related decreases (p < .05) in the semen and sperm parameters, testicular function indices, antioxidant activities and female rat fertility indices were reversed/ameliorated by AECDR. AECDR significantly altered the function indices of the liver and kidney and the lipid profile and selectively altered the haematological parameters. There was no treatment-related histoarchitectural changes in the organs. Overall, the aqueous extract of C. dependens roots exhibited pro-spermatogenic, fertility enhancing, antioxidant and androgenic activities in male rats. It also exhibited functional toxicity. Therefore, the chronic use of AECDR may not be completely safe as oral remedy.