Milletia aboensis has long-standing ethnopharmacological indications for the treatment of symptoms and diseases related to menopause. This investigation examined the effects of its phytoestrogen-rich fraction on some predictors of cardiovascular risk in an ovariectomized rat model of menopause. In vitro, antioxidant activity was determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH) test. Ovariectomy was used to trigger menopause by surgically removing the ovaries under anesthesia. After recovery, the animals were treated orally with the phytoestrogen-rich fraction (PERF) of M. aboensis daily for 30 days. Blood samples were obtained for the estimation of serum lipid profile, antioxidant enzyme activities, lipid peroxidation, and platelet count. The PERF showed the strongest inhibition of DPPH radical with an IC50 value of 19.65 µg/ml. At 200 and 400 mg/kg, the PERF dose-dependently showed significant increase in high-density lipoprotein (HDL) (42.86 and 43.05 mg/dl) and a significant (p < 0.05) decrease in low-density lipoprotein (LDL) levels (3.78 and 1.24 mg/dl) compared with the ovariectomized (OVX) control (31.82 and 20.32 mg/dl, respectively). Being dose-dependently, the PERF increased catalase (CAT) and superoxide dismutase (SOD) enzyme activities as well as significantly reduced malondialdehyde (MDA) levels compared to OVX control. At 200 and 400 mg/kg, the PERF restored platelet count with values (316.54 and 343.3 103/IU, respectively) close to that of sham-operated control (365.17 103/IU). The ability of M. aboensis to reverse lipid abnormalities associated with ovariectomy coupled with its reduced platelet count, and antioxidant effects make it a potential therapeutic phytoestrogen remedy for the management of cardiovascular complications associated with estrogen deficiency.