Nicotinamide adenine dinucleotide (NAD⁺) is a critical coenzyme involved in numerous enzymatic processes that regulate essential cellular functions, including energy metabolism. NAD⁺ levels are known to decline in metabolic disorders such as obesity, in both rodents and humans. Boosting NAD⁺ through supplementation with NAD⁺ precursors like nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) has consistently been shown to improve metabolic outcomes in preclinical models. Recently, their reduced forms—NMNH and NRH—have shown greater potency in elevating NAD⁺ levels in vitro and in vivo. However, their long-term effects on metabolic homoestasis and obesity pathogenesis remain largely underexplored. In this study, we investigated the impact of acute and chronic NMNH administration on metabolic parameters in a murine model of HFD-induced obesity. Acutely, NMNH produced more rapid and marked increases in NAD+ across multiple tissues, compared to other NAD+ precursors. Interestingly, NMNH also induced rapid depletion of liver glycogen. Twelve weeks of NMNH treatment via IP injection in HFD-fed mice significantly attenuated weight gain, resulting in final body weights comparable to chow-fed controls, while vehicle-treated HFD mice gained approximately 40% body weight. This effect was primarily driven by a reduction in adiposity, independent of food intake. NMNH also enhanced endurance in both dietary groups and improved insulin sensitivity in HFD-fed mice based on an index of insulin sensitivity. NMNH reduced triacylglycerol (TAG) and diacylglycerol (DAG) accumulation and oxidative stress markers in skeletal muscle, and decreased renal TAG content in HFD mice. Overall, NMNH has widespread metabolic effects, with promising therapeutic potential for addressing prevalent metabolic conditions such as obesity and type 2 diabetes.