Background. Curcumin shows great effects of inhibiting tumor cell proliferation, inducing apoptosis, inhibiting tumor metastasis, and inhibiting angiogenesis on a variety of tumors. However, the biological activity and possible mechanisms of curcumin in the treatment of retinoblastoma have not been fully elucidated. This study explored the potential therapeutic targets and pharmacological mechanisms of curcumin against retinoblastoma based on network pharmacology and molecular docking. Methods. The genes corresponding to curcumin targets were screened from the HERB, PharmMapper, and SwissTargetPrediction databases. Protein-protein interaction (PPI) networks were constructed for the intersecting targets in the STRING database. Cytoscape 3.7.0 was used for network topology analysis and screening of important targets. R 4.1.0 software was used for Gene Ontology (GO) function enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of intersection targets. The molecular structures of curcumin and core target proteins were obtained from PubChem and PDB databases, and the two were preprocessed and molecularly docked using AutoDockTools and PyMOL software. Results. Through network data mining, we obtained 504 curcumin targets and 966 retinoblastoma disease targets, and 44 potential targets for curcumin treatment of retinoblastoma were obtained by mapping. Three core targets were obtained from network topology analysis. 462 biological processes, 21 cellular compositions, and 34 molecular functions were obtained by GO enrichment analysis. KEGG pathway analysis revealed 94 signaling pathways, mainly involving chemical carcinogenesis-receptor activation, chemical carcinogenesis-reactive oxygen species, viral carcinogenesis, Th17 cell differentiation, etc. The molecular docking results indicated that the binding energy of curcumin to the core targets was less than 0 kJ mol−1, among which the binding energy of RB1 and CDKN2A to curcumin was less than −5 kJ mol−1 with significant binding activity. Conclusion. Based on molecular docking technology and network pharmacology, we initially revealed that curcumin exerts its therapeutic effects on retinoblastoma with multitarget, multipathway, and multibiological functions, providing a theoretical basis for subsequent studies.