Arsenic is a well-recognized environmental contaminant that occurs naturally through geogenic processes in the aquifer. More than 200 million people around the world are potentially exposed to the elevated level of arsenic mostly from Asia and Latin America. Many adverse health effects including skin diseases (i.e., arsenicosis, hyperkeratosis, pigmentation changes), carcinogenesis, and neurological diseases have been reported due to arsenic exposure. In addition, arsenic has recently been shown to contribute to the onset of non-communicable diseases, such as diabetes mellitus and cardiovascular diseases. The mechanisms involved in arsenic-induced diabetes are pancreatic β-cell dysfunction and death, impaired insulin secretion, insulin resistance and reduced cellular glucose transport. Whereas, the most proposed mechanisms of arsenic-induced hypertension are oxidative stress, disruption of nitric oxide signaling, altered vascular response to neurotransmitters and impaired vascular muscle calcium (Ca2+) signaling, damage of renal, and interference with the renin-angiotensin system (RAS). However, the contributions of arsenic exposure to non-communicable diseases are complex and multifaceted, and little information is available about the molecular mechanisms involved in arsenic-induced non-communicable diseases and also no suitable therapeutic target identified yet. Therefore, in the future, more basic research is necessary to identify the appropriate therapeutic target for the treatment and management of arsenic-induced non-communicable diseases. Several reports demonstrated that a daily balanced diet with proper nutrient supplements (vitamins, micronutrients, natural antioxidants) has shown effective to reduce the damages caused by arsenic exposure. Arsenic detoxication through natural compounds or nutraceuticals is considered a cost-effective treatment/management and researchers should focus on these alternative options. This review paper explores the scenarios of arsenic contamination in groundwater with an emphasis on public health concerns. It also demonstrated arsenic sources, biogeochemistry, toxicity mechanisms with therapeutic targets, arsenic exposure-related human diseases, and onsets of cardiovascular diseases as well as feasible management options for arsenic toxicity.