In the previous study, mixed ligand complexes of 2,2′-bipyridine (Bipy) and febuxostat (FEB) with Mn(II), Co(II), Ni(II), and Fe(III) ions (C1–C4) were synthesized and characterized for their antioxidant activity. In this study, the focus shifted to evaluating their potential as anti-colon cancer agents through MTT assays on HCT-116 colon cancer cells. The C3 complex showed the strongest inhibitory effect (IC50 = 6.19 ± 0.49 μg/mL), outperforming doxorubicin (IC50 = 98.36 ± 3.74 μg/mL). Toxicity was assessed using the shrimp lethality test, categorizing C1 as low toxicity, and C2, C3, and C4 as moderately toxic. Toxicity prediction models supported these findings, suggesting low toxicity via IM/IV and moderate toxicity via oral/subcutaneous routes. Molecular docking studies showed strong binding interactions, particularly for C3, with an affinity of 7.30 kcal/mol, indicating its high interaction potential. Moreover, binding free energy calculations, and MD simulations confirmed the stability of C3 (RMSD < 2 Å). Additionally, potential biological targets involved in cancer progression were identified using PharmMapper, SuperPred, and SwissTargetPrediction, including XDH, Cathepsin D, VEGFR2, CDK4, and PIK3CA, supporting the multi-target potential of these complexes. The study highlights the promising anticancer potential of Bipy-FEB-metal complexes, with C3 demonstrating the highest activity and moderate toxicity. These findings lay the groundwork for further therapeutic exploration of these compounds. = 7.26 ± 0.13 μg/mL), while C2 exhibited the least activity (IC50