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Colorectal cancer (CRC) and type 2 diabetes mellitus (T2DM) exhibit interrelated pathologies, yet the underlying mechanisms of their interaction remain largely elusive. GeGen-QinLian decoction (GQD) has shown therapeutic efficacy in both CRC and T2DM. This study aimed to elucidate the potential pharmacological mechanisms of GQD in the postoperative treatment of patients with CRC and T2DM. Transcriptomic data sets for CRC and T2DM were retrieved from The Cancer Genome Atlas and Gene Expression Omnibus databases. Differential expression analysis, univariate Cox regression analysis, and weighted gene coexpression network analysis were employed to identify shared genes between CRC and T2DM. Network pharmacology was used to analyze the bioactive components of GQD and their targets, identifying potential therapeutic targets for the concurrent treatment of T2DM and CRC. Enrichment analysis, immune infiltration assessment, and drug sensitivity analysis were performed, complemented by molecular docking to validate the affinity between potential targets and active components. A total of 433 shared genes between CRC and T2DM were identified, involving processes such as gene expression regulation, cell cycle control, apoptosis regulation, Wnt signaling pathway, regulation of NF-κB transcription factor activity, and inflammatory mediator regulation of transient receptor potential channels. We identified 204 bioactive components of GQD and 320 corresponding targets, of which 10 (ADRA1B [adrenergic receptor alpha 1B], CALM1 [calmodulin 1], CDKN2A [cyclin-dependent kinase inhibitor 2A], CTNNA1 [cadherin-associated protein], FCER2 [Fc fragment of IgE receptor II], GSR [glutathione reductase], GSTM1 [glutathione S-transferase mu 1], IL13 [interleukin 13], INSR [insulin receptor], and MAPK9 [mitogen-activated protein kinase 9]) were determined as potential targets for the treatment of T2DM and CRC using GQD. Enrichment analysis revealed that these targets were associated with pathways including insulin signaling pathway, cyclic guanosine monophosphate-protein kinase G signaling pathway, Ras signaling pathway, and Fc-epsilon receptor I signaling pathway. Molecular docking results demonstrated high affinity between these potential targets and active components, with the highest affinity observed between CALM1 and xambioona. This study systematically identified a set of shared genes between T2DM and CRC, along with the bioactive components and 10 potential targets of GQD for the treatment of T2DM and CRC. These findings provided a theoretical foundation for the combined therapy of T2DM and CRC.