Background and objective Eremomastax speciosa and Eremomastax polysperma plants potentially contain bioactive principles against reproductive toxicants and oxidative stress. Thus, the ameliorative action of methanol and ethyl acetate fractions of E. speciosa and E. polysperma leaves on cyclooxygenase-2 (COX-2) and oxidative-stressed states in indomethacin-induced rat tissues have been performed. Materials and methods The dried-leaf extract of E.speciosa and E. polysperma was subjected to liquid–liquid fractionation to obtain the ethyl acetate and methanol fractions. The ethyl acetate and methanol fractions were respectively administered orally to rats (200 mg/kg), 30 min, and 10 h after subcutaneous injection with indomethacin (5 mg/kg) for 4 days. The postadministration of E. speciosa and E. polysperma fractions was used to determine their effect on ovarian and serum COX-2 concentration, ovarian malondialdehyde, and ovarian nitric oxide concentrations. Results and conclusion E. speciosa and E. polysperma fractions significantly (P<0.05) increased the concentration of COX-2 in ovaries and serum compared with the group treated with indomethacin only. Malondialdehyde and nitric oxide concentrations were significantly (P<0.05) decreased in all the animal groups posttreated with plant fractions compared with indomethacin only. Histological assessment of the ovary showed proliferating ovarian follicles and mature Graafian follicles in the groups treated with the plant fractions, while the indomethacin-only group showed scanty primary follicles. These results showed that E. speciosa and E. polysperma leaf fractions mediated their protective effect on the ovaries and serum through the regulated COX-2 action and inhibited indomethacin-induced oxidative stress.