Neurodegenerative disease is a wide expression where the compilation of circumstances mainly affects neurons, which is a basic unit of the nervous system. Neurons are of utmost importance for brain function, however, like other cells of the body, they do not reproduce or replace once damaged. Neurodegenerative disease is a progressive disease which affects movement and mental functions, affecting approximately 30 million individuals worldwide. Alzheimer’s, Parkinson’s, Huntington’s and amyotrophic lateral sclerosis diseases are examples of this condition. These diseases are characterized by separate etiologies with distinct morphological and pathophysiological features. There are many evidences that suggest that these disorders arise by multi-factorial conditions such as oxidative stress, mitochondrial dysfunction, and/or exposure to metal toxicity and pesticides. The role of metals in neurodegenerative diseases has been widely considered as an underlying cause and, several studies pinpoint the toxic effects of metals. Metals are elements of air, water, and ecosystem. Although metals are vital components, however excessive accumulation of this element causes detrimental effects such as aluminum has been controversially invoked as an aggravating factor or cofactor in Alzheimer’s disease as well as in other neurodegenerative diseases, Manganese exposure can play an important role in causing parkinsonian disturbances, possibly enhancing physiological aging of brain in conjunction with genetic predisposition. In this review, we explore the effects of metals in two of the most common neurodegenerative diseases, Alzheimer’s and Parkinson’s disease and clinical effects of synthetic drugs and herbal medicines for these neurodegenerative diseases.