Oral squamous cell carcinoma (OSCC) is one of the most prevalent forms of oral malignancies, and its treatment procedures include surgery, radiation therapy, and chemotherapy. However, patients experience various adverse effects, and sometimes the treatment becomes ineffective due to resistance, leading to recurrence. Syzygium cumini, a plant with high medicinal value, such as antioxidant, anticancer, and antimicrobial properties, was used in this study against OSCC. The study aims to investigate the potential pharmacological mechanisms of S. cumini in the treatment of OSCC using a network pharmacology approach, molecular docking, and MD simulations. The active phytochemicals of S. cumini were collected using the IMPPAT database and filtered using SwissADME. Further, their respective targets were collected using SwissTargetPrediction. OSCC targets were retrieved from the GeneCards database, and their common targets were identified using a Venn diagram. The PPI network was built using STRING and Cytoscape. Subsequently, the core targets were obtained using MCODE, while the gene-disease-associated targets were obtained via DisGeNET. Molecular docking and simulations were performed for the protein-ligand complexes. The potential targets identified from the PPI networks include MAPK1, PTGS2, ESR1, MMP9, and PARP1. Molecular docking revealed that the MMP9-Geranyl butyrate, PTGS2-Ledol, and ESR1-(-)-Globulol complexes exhibited the highest binding affinities. MD simulation confirmed that these compounds exhibited strong, stable interactions, as well as compactness, with their corresponding targets. We identified the key compounds Geranyl butyrate, Ledol, and (-)-Globulol from S. cumini that effectively bind to OSCC targets and might play a vital role in the treatment.