Transcendental experience during yoga and meditation is well known for centuries. Here we discussed the safe and scientific process of transcendental experience. We also discussed neuroscience of transcendental experience during meditation. How to achieve transcendental experience? What are the risks in transcendental experience? Is it possible to transcend the limits of the material universe and entered into the realm of infinite? What are the brain dynamics and brain network connectivity during during transcendental experience? These are the few questions that I tried to explain in this article. True transcendental experience increases gray matter in the brain. It activates the prefrontal cortex—the newest part of the human brain. It creates many new pathways in the brain. The right insular cortex in the brain is activated by true transcendental experience. The insular cortex involved in compassion. moral decision making and pain control. The cortical thickness of the brain increases. Reduces the amyagdal activity in the brain.