The world today, is being ravaged by the emergence and re-emergence of microbial infections caused by antimicrobial-resistant strains, brought about primarily by the frequent and perhaps unnecessarily used antimicrobial agents. A need therefore arises to develop new antimicrobial drugs that can combat these pathogens resistant to currently available antibiotics. This present study has adopted a multi-enzyme in silico approach in its evaluation of new 2-pyrazolines as antimicrobial agents, by targeting and aiming to inhibit three pivotal enzymes in the bacteria’s life cycle. A library of fifty 2-pyrazolines was tailored to achieve the desired activity. The library of compounds and amoxicillin, a standard antimicrobial drug, were docked into the molecular target enzymes. They were also subjected to toxicity and ADME tests, using PROTOX and swissADME respectively. A moderate toxicity profile was indicated, as more than 90% of the ligands were in ProTox class 4. The majority exhibited advantageous ADME characteristics. A significant number of them demonstrated a binding affinity for the target proteins that was stronger than both the native ligand and the binding affinity of amoxicillin. Ligands 30, 20, and 19 are the notable ones across all target enzymes. These results suggest that these novel ligands may be powerful inhibitors, particularly when it comes to interfering with the formation of bacterial cell walls, folic acid, and nucleotide metabolism. Additional in vivo and in vitro research is required to confirm these results and evaluate their therapeutic potential.