Adrenoleukodystrophy (ALD) is a rare neurodegenerative disorder characterized by progressive demyelination and chronic neuroinflammation, particularly in the severe childhood cerebral form known as childhood cerebral adrenoleukodystrophy (CCALD). Neuroinflammatory signaling plays a critical role in disease progression; however, the molecular mechanisms involved remain incompletely understood. This study employed an integrated transcriptomic and computational framework to identify key inflammatory targets associated with ALD and evaluate the potential therapeutic compounds derived from medicinal plants. RNA-seq transcriptomic datasets from X-linked ALD and CCALD conditions were analyzed to identify differentially expressed genes (DEGs) linked to inflammatory pathways. Protein-protein interaction network analysis revealed Tumor Necrosis Factor-alpha (TNF-α) as a highly connected hub gene involved in neuroinflammatory regulation. Based on these findings, bioactive compounds derived from medicinal plants, such as Withania somnifera, Bacopa monnieri, Centella asiatica, and Tinospora cordifolia, were computationally screened to identify potential TNF-α modulators. Molecular docking analysis demonstrated favorable binding interactions for several compounds, while pharmacokinetic evaluation prioritized ashwagandhanolide as a promising candidate. To further investigate complex stability, a 500 ns molecular dynamics simulation was performed, followed by trajectory analyses, including RMSD, RMSF, radius of gyration, hydrogen bond profiling, and free energy landscape evaluation. The simulation results indicated a stable interaction between TNF-α and Ashwagandhanolide under physiological conditions. Binding free energy estimation using MM/PBSA further supported this interaction, with a calculated ΔG value of −18.22 kJ/mol. These findings highlight TNF-α as an important inflammatory target in ALD and suggest that medicinal plant-derived compounds may provide promising therapeutic strategies for neuroinflammatory modulation, supporting future experimental validation and translational research on this topic.