Nicotinamide adenine dinucleotide phosphate (NADPH) is a coenzyme that plays a crucial role in various cellular processes, including detoxification, biosynthesis of lipids and nucleotides, and the regeneration of cellular antioxidants. Oxidative stress occurs when there is an imbalance between the production of reactive oxygen species (ROS) and the body’s ability to detoxify them. NADPH is a vital component of the cellular antioxidant defense system, as it helps to regenerate antioxidants and neutralize ROS. Dysregulation of NADPH-generating enzymes can lead to increased oxidative stress, which is implicated in various cardiovascular diseases. Numerous studies have demonstrated the therapeutic value of NAD+ in cardiovascular disease. Compared to NAD+, there are fewer research on the cardiovascular effects of NADPH. This chapter will outline the research progress of NADPH and evaluate its potential in both as causative and curative agent for cardiovascular disease. Strategies aimed at modulating NADPH-dependent pathways may hold the potential for the prevention or treatment of heart diseases.