In Southern Nigeria, the leaves of Emilia coccinea (Sims) G Dons are used traditionally for birth control. This study was therefore aimed at evaluating the activities of the methanolic leaf extract of Emilia coccinea (EM) on parameters that affect reproduction as well as the acute toxic effects of the plant using nonpregnant female mice models. Leaves of EM were extracted by maceration with 99.8% methanol. Oral acute toxicity profiles were examined. The effects of EM on female reproductive cycle were determined after oral treatment with EM at 1000 and 100 mg/kg/day daily for 6 days using stilbesterol (1 mg/kg/day) and normal saline as controls. The activities of EM (1000 mg/kg/day and 100 mg/kg/day p. o) on reproductive hormones and organs were also studied using estradiol valerat (100 mg/kg/day p.o), progesterone (10 mg/kg/day s.c.), and normal saline as controls. The extract did not induce any observable toxic effect after 24 h. At 1000 mg/kg, the extract significantly shortened the estrus cycle (P < 0.05) while prolonging the estrus phase which were comparable to that observed with stilbesterol. The extract also increased uterine weight and altered the histology of uterine and ovarian tissues. The female reproductive hormones were additionally altered at 1000 mg/kg and the effects were comparable to that of estradiol valerat such as to indicate possible antifertility effects. LC-HRFTMS analysis showed 9 putatively identified compounds with pyrrolizidine alkaloid occurring at the highest intensity among the identified compounds. In conclusion, the leaf extracts of EM has been shown in this study to exhibit antiovulatory and estrogenic activities which would support the traditional use of the plant in Nigeria.