Hypertension is a multifaceted, polygenic, as well as complex disorder that has become a foremost origin of premature mortality worldwide, significantly surging the risk of developing stroke and other cardiovascular diseases (CVDs). Although the precise pathology remains unidentified in the majority of clinical cases, oxidative stress driven by the elevated level of reactive oxygen species (ROS) has emerged as a centrally acting pathology of hypertension. Among the various enzymatic sources of ROS, nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOX), especially NOX1, NOX2, NOX4, and NOX5, play essential roles in the cerebrovascular system. Enzymatic hyperactivation instigates the generation of ROS and interferes with redox-sensitive intracellular mechanisms, including ER stress, leading to vascular endothelial remodeling and inflammation. ROS also interferes with deviant signaling cascades by destroying vascular integrity and organ function. The elevated ROS generation fosters an inflammatory environment that contributes to hypertension, both the causes and consequences of sustained hypertension. Preclinical findings consistently emphasized that ROS scavengers reduce systemic pressure and mitigate the harmful effects on vascular system; antioxidant therapies in clinical practice have showcases promising findings, emphasizing the complex mechanism in redox pathology in hypertension. This chapter intended to explore the intricate interplay between ROS generation, intracellular redox signaling-mediated inflammation in hypertension. It also emphasizes the significance of NOX enzymes as major ROS sources, outlines the molecular pathways underpinning oxidative stress, and explores their systemic effects on CVDs, including hypertension. Understanding these mechanisms offers potential for novel therapeutic strategies targeting oxidative stress and inflammation in hypertensive patients.