Alchornea cordifolia is used traditionally for the treatment of infertility and venereal diseases. Thirty rats were randomly divided into five groups of six rats each: Group 1 (distilled water), group 2 (7 mg/kg sodium arsenite), group 3 (7 mg/kg sodium arsenite and 100 µg/kg polyphenol‐rich fraction 1 of A. cordifolia), group 4 (7 mg/kg sodium arsenite + 100 µg/kg polyphenol‐rich fraction 2) and group 5 (7 mg/kg sodium arsenite + α‐tocopherol). The experiment lasted 30 consecutive days. Biochemical markers of oxidative stress and antioxidants, male reproductive hormones, spermatozoa function tests, histopathology, immunoreactivity of androgen receptor binding protein (ARBP) and anti‐apoptotic B‐cell lymphoma‐2 protein expressions were estimated. Data were analysed using descriptive statistics and ANOVA at p < .05. Treatment with AF1 significantly decreased markers of oxidative stress, but increased the systemic antioxidants, testosterone, FSH, spermatozoa count and motility. Histopathological lesions of necrosis and germinal epithelial sloughing observed in sodium arsenite group were absent in sodium arsenite + 100 µg/kg polyphenol‐rich fraction 1 group. Expressions of androgen receptor binding protein and anti‐apoptotic B‐cell lymphoma‐2 were highest in sodium arsenite + 100 µg/kg polyphenol‐rich fraction 1 group. In conclusion, the polyphenol‐rich fraction of A. cordifolia is protective against sodium arsenite‐induced infertility in male rats through the inhibition of oxidative and apoptotic mechanisms.