Independent supplementation with nitrate (NIT) and resveratrol (RSV) enrich various aspects of mitochondrial biology in key metabolic tissues. While RSV is known to activate Sirt1 and initiate mitochondrial biogenesis, the metabolic benefits elicited by dietary nitrate appear to be dependent on AMPK-mediated signalling events, a process also linked to the activation of Sirt1. While the benefits of individual supplementation with these compounds has been characterized, it is unknown if co-supplementation may produce superior metabolic adaptations. Thus, we aimed to determine if treatment with combined +NIT and +RSV (+RN) could additively alter metabolic adaptations in the presence of a high-fat diet (HFD). Both +RSV and +NIT improved glucose tolerance compared to HFD (p<0.05), however, this response was attenuated following combined +RN supplementation. Within skeletal muscle, all supplements increased mitochondrial ADP-sensitivity compared to HFD (p<0.05), without altering mitochondrial content. While +RSV and +NIT decreased hepatic lipid deposition compared to HFD (p<0.05), this effect was abolished with +RN, which aligned with significant reductions in Sirt1 protein content (p<0.05) following combined treatment, in the absence of changes to mitochondrial content or function. Within eWAT, all supplements reduced crown-like structure accumulation compared to HFD (p<0.0001) and mitochondrial ROS emission (p<0.05), alongside reduced adipocyte CSA (p<0.05), with the greatest effect observed following +RN treatment (p=0.0001). While the present data suggests additive changes in adipose tissue metabolism following +RN treatment, concomitant impairments in hepatic lipid homeostasis appear to prevent improvements in whole-body glucose homeostasis observed with independent treatment, which may be Sirt1-dependent.