Monosodium glutamate (MSG) at high concentration has been reported to alter the physiological and biochemical states of animals and humans. Ganoderma lucidum (G. lucidum) is a polypore mushroom reported to possess many medicinal attributes such as anticholesterolemia and the control of hormonal disorders. The present study investigated the effect of water extract of G. lucidum in the changes of haematology, oestradiol, cholesterol and protein levels of Wistar rats induced by MSG. Haematological analysis was determined from plasma, while oestrogen, serum total protein and cholesterol levels were determined from the serum of the rats. Results showed that MSG significantly raised the level of oestrogen (62.5 ± 0.28 pg/mL) in the rats which was significantly reduced in the rats fed with MSG for 30 days before treating them with the extracts of G. lucidum (30.85 ± 12.94 pg/mL–44.15 ± 0.92 pg/mL) and in rats fed concurrently with MSG and G. lucidum. The cholesterol level was significantly reduced in the rats treated with MSG and G. lucidum (200 mg/kg) concurrently compared to rats fed with MSG alone. The white blood cell (WBC) and red blood cell (RBC) levels were within normal in rats fed with both MSG and G. lucidum as in the control group while the rats fed with MSG only had low WBC, neutrophil (NEU) and RBC. This could imply that G. lucidum ameliorates the effect of MSG on serum oestrogen, serum cholesterol, WBCs, NEU, platelets and lymphocytes.