Curcuma comosa was reported to have uterotrophic effects in ovariectomized (OVX) rats. The present study aims to investigate the plant estrogenic-like effects of C. comosa hexane extract on spatial memory and estrogen receptors (ER) in the hippocampus. Female rats received 5 days' Morris water maze training before the ovariectomy, followed by the daily intraperitoneal administration of C. comosa hexane extract at a dose of 250 and 500 mg/kg body weight for 4 weeks. Estradiol (10 μg/kg body weight) was used as the positive control. OVX significantly increased the latency of the animal to the platform, while estradiol and both doses of C. comosa hexane extract reversed the memory impairments. By using the reverse transcription polymerase chain reaction technique, C. comosa hexane extract was shown to produce a selective increase of the ER alpha subtype but not beta subtype in hippocampus, while estradiol increased both of them. C. comosa did not affect spatial memory, learning ability, and ER mRNA levels in the sham OVX rats. In conclusion, C. comosa hexane extract improved the spatial memory of the OVX rats, which was similar to estrogen. The influence on the memory changes might be selectively related to ER alpha in the hippocampus.