A series of chloroacetamide derivatives (1-22) was synthesized to address the urgent need for new antimicrobial and antioxidant agents. The chemical structures were confirmed by 1H-NMR, 13C-NMR and MS spectroscopic analyses. Most compounds inhibited in vitro Gram-positive bacteria S. aureus and B. cereus as well as Gram-negative bacteria (E. coli and P. aeruginosa) and yeast (C. albicans). Interestingly, compound 13 showed the broadest spectrum, especially against B. cereus (MIC = 10 mg/L). Compounds 6 and 20 displayed potent activity against C. albicans (EC50 = 197.02 and 189.13 mg/L, respectively). All compounds exhibited antioxidant activity, with 14 compounds surpassing α-tocopherol (standard) in DPPH radical scavenging. In silico analyses were conducted using molecular docking, drug-likeness data, physicochemical properties, and ADMET parameters to evaluate the potential of the compounds. Molecular docking simulations against the active sites of NADPH oxidase, penicillin-binding protein (bacterial target), and lanosterol 14-alpha demethylase (fungal target) revealed favorable binding energies for the majority of the compounds, indicating good affinity towards the targeted proteins. Overall, the research on novel multifunctional chloroacetamide derivatives is a valuable contribution to the field of biological chemistry and has the potential to lead to the development of new and improved products for a variety of microbes.