Adherence to prescribed psychiatric and nonpsychiatric medicine is a severe problem among people with mental illnesses, it led to negative health effects. Anxiety is how your brain responds to stress and warns you of impending danger. The most common treatments for anxiety are to avoid alcohol, reduce caffeine intake, do physical exercise, quit smoking, stress management etc. Anti-anxiety drugs mostly are alprazolam, clonazepam, chlordiazepoxide, diazepam and lorazepam. Ayahuasca is a plant-based psychedelic. Psychedelics affect all the senses, altering a person’s thinking, sense of time and emotions. The active chemical in ayahuasca is DMT (dimethyltryptamine). DMT targets the serotonin receptors in the brain, working similarly to anti-anxiety. Human enzymes, particularly monoamine oxidase (MAO) and hepatic P450s break down DMT relatively quickly. The most crucial aspect of monoamine oxidase from a clinical perspective is that it is so active and quick that if someone takes DMT orally, which is the main method of administration, by the time it reaches the liver, monoamine oxidase will have eliminated all of it before it can have any biological effects. Therefore, to have a biological effect, one must either consume a large amount of DMT, which is not advisable or the alternate and best way is to bypass the liver. The transdermal drug delivery system (TDDS) offers a desirable alternative to oral drug administration, avoids the liver's first-pass metabolism. This review briefly describes the effect, advantages and disadvantages of ayahuasca which contains DMT in active form, by Transdermal route in the treatment of anxiety.