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Background: Stroke, particularly ischemic stroke, is one of the leading causes of death worldwide. Ischemic stroke causes a failure of oxidative phosphorylation and ATP synthesis, resulting in high levels of reactive oxygen species (ROS), neuroinflammatory responses, and apoptosis, all of which result in cell death. Neuroprotective agents are given to prevent the infarct area from expanding. Objective: This study aims to predict an in silico interaction by 7,8-dihydroxyflavone as neuprotective agent through TrkB signaling and inhibiting Glutaminase activity. Methods: In silico simulation with 7,8-dihydroxyflavone (DHF) as neuroprotective agent using PubChem, RCSB, Biovia Discovery Studio, PyRx, and PyMol software. This study analyzes the pharmacokinetics, pharmacodynamics, and protein-ligand interactions between 7,8-DHF as a ligand with TrkB (4AT5) and Glutaminase (5JYO) as protein target, compared to their native ligand. Results: 7,8 DHF binds to 4AT5 and 5JYO with lower bond energy (-9.4 Kcal/mol and -6.3 Kcal/mol, respectively) than the native ligand (-5 Kcal/mol and -5.9 Kcal/mol, respectively). It means that 7,8-DHF may increase protective mechanism. Conclusion: These findings tend to increase downstream signaling pathways, leading to increased TrkB expression, which induces protective mechanisms, and decreased glutamate expression, which reduces glutamate toxicity.