Objective. Oral submucous fibrosis (OSMF) is a chronic, fibrotic disease that affects the oral cavity, showing a high rate of malignant transformation. Curcuma exerts therapeutic potentials in many diseases including OSMF. However, the potential targets and pathways to explain the therapeutic effects of curcuma on OSMF are outside the scope of present knowledge. Herein we intend to reveal the predictive targets and potential pathways of curcuma against OSMF by a network pharmacology-based approach followed by molecular docking technology. Methods. We searched the SymMap, GeneCards, and OMIM database to obtain curcuma and OSMF common targets. The protein-protein interaction (PPI) of curcuma and OSMF common targets were then analyzed, followed by functional enrichment analysis. The best binding mode of curcuma and target proteins was analyzed by molecular docking technology. Results. We collected 290 putative targets of curcuma molecules and 600 known therapeutic targets of OSMF, with 64 curcuma and OSMF common targets sorted out. In the PPI network, there were 63 nodes with 922 edges. The node indicates protein and the line indicates PPI relation. The most enriched GO term in the BP level is “gland development”, followed by “cellular response to chemical stress”, and then “response to oxygen levels”, while the most enriched GO term in CC and MF is “membrane raft” and “cytokine receptor binding”, respectively. We also found 131 KEGG pathways significantly enriched by curcuma and OSMF common targets. The binding energy of curcuma to ALB, TNF, TP53, IL6, and VEGFA was −9.5 kcal/mol, −3.9 kcal/mol, −3.5 kcal/mol, −3.6 kcal/mol, and −8.9 kcal/mol, respectively, which suggested ALB and VEGFA were regarded as main targets involving in the potential mechanism of curcuma against OSMF. Conclusion. The present study illustrated that the therapeutic effects of curcuma on OSMF were achieved by targeting ALB and VEGFA, which giving reference to further drug design and development for OSMF.