Polypharmacology is a design or use of pharmaceutical agents in which single drug is used to treat multiple diseases. Aquaporin proteins are identified to treat migraine with aura and brain edema. This study focuses on Aquaporin-1 and Aquaporin-4. AQP-1 is expressed in small afferent sensory nerve fibers. Over-expression of peripheral nervous system causes migraine.AQP-4 is an abundant channel water protein in brain that regulates water transport to prevent homeostasis. Over-expression of AQP-4 contributes to water imbalance in ischemic pathology resulting in cerebral edema. Purpose of this study is to identify a potent inhibitor for the treatment of migraine with aura and brain edema.As in the recent studies, no conventional methodologies have been focused through the approach of polypharmacology. Structures of AQP-1 and AQP- 4 proteins were retrieved from PDB (Protein Data Bank). PyRx software was used to perform molecular docking.Analogues of ligands were analyzed which contained significant similarities of associated proteins to get efficient inhibitor. Toxicity of lead compound was measured through admetSAR. A lead compound was predicted to treat these diseases.