Kratom (Mitragyna speciosa) is a medicinal plant grown wildly in Southeast Asian. It has been used traditionally for its analgesic and relaxing effects after hard day of labors. The main alkaloid of kratom, mitragynine binds to opioid receptors to give opioid-like effects, therefore it has been widely utilized as opiate substitute. Long term usage of kratom lead to addiction and has been associated with death. Although rural folks of Southeast Asia are still consumed kratom for its beneficial values. Currently, abused of kratom is identified by the presence of mitragynine in the user's urine. Nevertheless, since kratom are still in used for its stimulating effect, the presence of mitragynine in urine cannot differentiate between chronic user for its opiate-like effect with occasional user for its medicinal effect. In view of the rise of addiction cases to kratom, a method able to detect kratom addiction is greatly needed. Given that drug addiction is a dynamic behavioral and physiological process, the current advancement of proteomic techniques will be able to use for analyzing the expression and alteration of proteins upon addiction to kratom, which concurrently will provide a more thorough knowledge of addiction pathophysiology.