Background Mood and memory deterioration occurs after ovariectomy (OVX) with various degrees and sometimes requires medical intervention. Menaquinone-7 (MK-7) is a potent isoform of vitamin K2 and has many effects on the bone and cardiovascular system. However, the effect of MK-7 on the brain and its mechanisms of action are still unclear. This study was performed to investigate the effect of MK-7 on mood and memory disorders following ovariectomy. Thirty-two female albino rats were divided into four groups (n=8). Group I (control group) included shamoperated rats with sunflower oil intake. Group II (K2) included sham-operated rats with an intake of MK-7 dissolved in sunflower oil. Group III (K2 OVX) included ovariectomized rats with an intake of MK-7 dissolved in sunflower oil. Group IV(OVX) included ovariectomized rats with sunflower oil intake. Working memory, anxiety, depression, and sociability behaviors were investigated in all groups. Gene expression of BAX, BCL2, and p53 was measured in the hippocampus of all groups by real-time PCR. Besides, BAX/BCL2 ratio was calculated. Results Working memory, anxiety, depression, and sociability behaviors in the OVX rats showed a significant change compared to the sham-operated. However, the intake of MK-7 after the OVX resulted in significant improvement. Regarding hydrogen peroxide and MDA activity, they were significantly higher in the OVX group compared to the sham-operated groups, while in the K2OVX group, their activity showed a significant decrease in comparison with the OVX group. However, catalase and total antioxidant capacity were significantly lower in the OVX group compared to the sham-operated group, while in the k2OVX group, their activity showed a significant increase in comparison with the OVX group. The OVX group showed a significant elevation in the BAX, BAX/BCl2 ratio, and P53, but BCL2 was significantly reduced. However, the intake of MK-7 caused a significant improvement. Conclusions Our study showed that the OVX group showed significant physiological, biochemical, and molecular changes, which can be prevented by MK-7 intake.