Polycystic ovary syndrome (PCOS), one of the important endocrine disorders affecting females in the reproductive age, is caused mainly by an abnormal oxidation status that subsequently causes inflammatory conditions. Thus, this study aims to examine the possible individual prophylactic effects of gasotransmitters, hemin, or L‐arginine in letrozole‐induced PCOS. Fifty adult female albino rats were used and separated into a control group, which received the vehicle; a letrozole‐induced PCOS group (L), which received letrozole orally at a dose level of 1 mg/kg for 21 days; a letrozole+hemin (L+H) group, which received letrozole plus hemin at a dose level of 25 mg/kg injected IP twice per week for 21 days; and a letrozole+L‐arginine (L+A) group, which received letrozole plus L‐arginine at a dose level of 200 mg/kg orally for 21 days. During PCO induction, the body weight and Lee index were measured. Serum glucose, insulin, lipid profile, gonadotrophic hormones, testosterone, estrogen, and tumor necrosis factor alpha were assayed, while ovarian tissues were analyzed to measure the oxidative state and histopathological changes. Our results proved that either hemin or L‐arginine administration could improve the oxidative state, the inflammatory reaction, the hormonal imbalance, and the metabolic disturbances in PCO rats, which was confirmed by a histopathological examination of the rats’ ovaries. In conclusion, either hemin or L‐arginine had protective effects against PCOS with better pathophysiological changes with hemin.