Natural products are a great group of secondary metabolites produced by living organisms to optimize nature. Natural sources such as terrestrial higher plants, fungi, bacteria, and marine organisms synthesize the metabolites to adapt the their microenvironments. To date, many FDA approved drugs have been discovered for therapeutic use from natural sources, including taxol (paclitaxel), vincristine/vinblastine (anticancer), fingolimod (multiple sclerosis), cyclosporine and doxorubicin (immunosuppressant). Nowadays, naturally occurring compounds are a great reservoir for drug discovery and design. In the present study, we have focused on potential modulatory activities of triterpenoid-based natural products and their derivatives by Click Chemistry towards epidermal growth factor receptor (EGFR) protein through computed-aided screening. Our findings revealed that azole derivatives of betulinic acid and ursolic acid showed significantly binding affinity on EGFR protein by molecular docking.