Generalized Anxiety Disorder (GAD) presents a significant burden on individuals and society, necessitating the exploration of effective treatments. Sphaeranthus indicus Linn, known as the "East Indian Globe Thistle," has gained attention due to its traditional use in alleviating anxiety. In Ayurveda, it’s recognized for its mental health benefits and categorized as a "Medhya Rasayana," indicating its potential to reduce anxiety and enhance cognitive function. Various dosage forms of Sphaeranthus indicus L. are employed in Ayurvedic practice, highlighting its versatility and efficacy in addressing diverse health concerns.Phytochemical analysis reveals compounds like flavonoids, alkaloids, and polyphenols in Sphaeranthus indicus L., which may act synergistically to modulate neurotransmitter systems and oxidative stress pathways, potentially alleviating anxiety. Molecular docking and dynamics simulations will investigate these interactions with key anxiety-related targets like GABA and serotonin receptors, providing insights into their anxiolytic mechanisms.To validate in-silico findings, clinical studies involving GAD-diagnosed participants will assess Sphaeranthus indicus L.’s safety and efficacy compared to placebos or standard anxiolytic medications. Objective measures such as anxiety scales and physiological parameters will gauge treatment outcomes.This multidisciplinary approach integrates traditional herbal wisdom with modern scientific methodologies, aiming to provide alternative treatments for GAD. If proven effective, Sphaeranthus indicus L. could offer a natural and safer alternative to synthetic drugs, potentially improving the quality of life for GAD sufferers. By synthesizing in-silico predictions with clinical assessments, this research seeks to comprehensively evaluate the therapeutic potential of Sphaeranthus indicus L., opening new avenues for GAD management.