PurposeHere, we studied the beneficial effects of aerobic exercise on metabolic syndrome components, cognitive performance, brain derived neurotrophic factor (BDNF) and irisin in ovariectomized rats with different serum vitamin D (Vit D) status.MethodsEighty female wistar rats were divided into 2 groups of sham operated (sham, n = 8), and ovariectomized (OVX, n = 72). Then OVX were divided into 9 groups of receiving combination of exercise protocol with low dose of Vit D (OVX + EXE + LD), high dose of Vit D (OVX + EXE + HD), Vit D deficiency (OVX + EXE − D), and (OVX + EXE + Veh). Also non exercised groups of OVX receiving high dose of Vit D (OVX + HD), low dose of Vit D (OVX + LD), Vit D deficiency (OVX − D), and Veh (OVX + Veh) were included. After 2 months of related interventions, spatial memory was assessed using Morris water maze (MWM), and then metabolic syndrome components were measured.ResultsHigh dose of Vit D supplementation showed significant reduction in weight (p = 0.001), lipid profiles (p = 0.001), visceral fat (p = 0.001) and waist circumference (p = 0.001) regardless of exercising or not, with no change in cognitiive function. Serum BDNF level was significantly higher in Vit D deficient group (p = 0.001), and was decreased in the OVX + HD. In contrary, irisin did not show any significant relationship with serum concentration of Vit D, while it was significantly elevated in the exercised groups compared with non-exercised counterparts.ConclusionVit D insufficiency deteriorates metabolic syndrome components, and elevates serum BDNF as a compensatory metabotropic factor, and further supplementation significantly attenuates these components parallel with reduction in BDNF. In addition, aerobic exercise successfully induces various metabolic benefits, provided optimum serum level of Vit D.