We aimed to explore the neuroprotective efficacy of Yashtimadhu powder, prepared from the roots of Glycyrrhiza glabra L. (https://mpns.science.kew.org; http://www.ayurveda.hu/api/API-Vol-1.pdf) commonly known as licorice, a known Medhya rasayana in the Indian Ayurvedic texts against Parkinson’s disease. To test the efficacy of Yashtimadhu powder, we used rotenone to generate an in vitro PD model using retinoic acid-differentiated IMR32 cells. Yashtimadhu powder (Lot No.64) was procured from SDP Remedies and Research Centre, Mangalore, India, a GMP-certified Ayurvedic product manufacturer ((http://sdpayurveda.com/products/choorna/yastimadhu-choorna/)The Yashtimadhu neuroprotection was ascertained using cell cytotoxicity, activation of apoptotic proteins and kinases. We used Tandem mass tag (TMT)-lables to understand the differentially regulated proteins across various treatment groups, using Orbitrap Fusion Tribrid mass spectrometer. The mass spectrometry data is acquired in biological duplicates and technical triplicates. We report 4,864 proteins corresponding to 4,783 gene symbols. The proteins were filtered out based technical and biological replicate concordance, thereby reporting 3,720 proteins common among the biological replicates.