Background & Purpose: We have earlier shown that vitamin D deficiency induces heart failure, in part, through insulin resistance. Whether activation of vitamin D receptor can attenuate heart failure, associated with metabolic syndrome, requires investigation. We aimed to assess cardioprotective potential of paricalcitol, a vitamin D receptor-activator, in high fat high fructose-fed rats. Experimental approach: Male Sprague Dawley rats were fed with control (Con) or high fat high fructose (HFHFrD) diet for 20 weeks. After 12 weeks, rats from HFHFrD group were divided into: HFHFrD, HFHFrD+P (paricalcitol i.p. 0.08 ug/kg/day) and HFHFrD+E (enalapril maleate i.p. 10 mg/kg/day). Intraperitoneal glucose tolerance test, blood pressure measurement and 2D echocardiography were performed. Cardiac fibrosis was assessed in Masson trichrome-stained paraffin-embedded heart sections. Mitochondrial DNA and proteins, and citrate synthase activity were measured in rat hearts. VDR was silenced in H9c2 cardiomyoblasts and immunoblotting was performed. Key Results: Paricalcitol improved glucose tolerance, serum lipid profile and blood pressure in high fat high fructose-fed rats. Paricalcitol reduced cardiac wall thickness, and increased ejection fraction in high fat high fructose-fed rats, with no effect on perivascular fibrosis. PGC1-α was uprgulated in HFHFrD+P group compared to HFHFrD group, without significant difference in mitochondrial content. Citrate synthase activity was significantly higher in HFHFrD+P group compared to HFHFrD group. Rat hearts of HFHFrD+P group had significantly higher expression of mitofusins. H9c2 cells with VDR knockdown showed significantly lower expression of Mfn2. Conclusion & Implications: Paricalcitol is cardioprotective in rats with metabolic syndrome, through improved mitochondrial dynamics, indicating repurposing potential.