Cancer remains a major global cause of death, driving the continuous search for innovative and effective treatments. In this context, we synthesized a series of 10 new hybrid compounds (M1–M10) by combining metformin (MET), a widely used anti-diabetic drug with emerging anti-cancer properties, and 10 different phenolic acids (A1–A10), known for their antioxidant and anti-cancer effects. To investigate their potential, we selected two target enzymes implicated in cancer progression—arachidonate 5-lipoxygenase (Protein Data Bank ID: 7TTL) and matrix metalloproteinase 9 (MMP9; PDB ID: 1GKC)—for molecular docking using AutoDock 4.2. Based on drug-likeness predictions and docking results, we further performed 100-nanosecond molecular dynamics simulations in GROMACS 2022 on four complexes—MMP9–A3, MMP9–M3, MMP9–MET, and MMP9–marimastat—to assess their stability and interactions at the atomic level. In comparison with individual phenolic acids (−6 to −8 kcal/mol), MET (−6 to −8 kcal/mol), and the reference inhibitor marimastat (−5 kcal/mol), the synthesized hybrids showed greater binding affinities, ranging from −7 to −10 kcal/mol, according to molecular docking studies. Molecular dynamics simulations, evaluated through parameters, such as root-mean-square deviation, root-mean-square fluctuation, radius of gyration, and hydrogen bond interaction profiles, demonstrated that the MMP9–M3 complex showed superior stability, higher drug-likeness, and lower predicted toxicity compared with the other studied complexes. Overall, the results indicate that the synthesized hybrids, especially M3, are the most promising candidates in the series. In conclusion, the design of hybrid compounds appears to be a practical approach for discovering novel phytochemical-based anti-cancer agents. In addition, the use of bioinformatics tools is crucial for streamlining the identification of the most promising lead compounds and optimizing experimental outcomes.