BACKGROUND: 8-Hydroxyquinoline and 4-thiazolidinone derivatives are promising antimicrobial agents, recognized for their activity against resistant pathogens. AIM: The aim of this study is to develop 8-hydroxyquinoline-4-thiazolidinone derivatives as potential antimicrobial agents. METHODS: Using a one-pot reaction with sodium tetrafluoroborate as an efficient and eco-friendly catalyst, compounds 6a - l were synthesized and subsequently screened for antibacterial and antifungal activity. Additionally, molecular docking and molecular dynamic simulations were performed to evaluate the active compounds and gain deeper insights into their potential as antimicrobial agents. RESULTS: Compounds 6f and 6 g showed superior antibacterial activity to ciprofloxacin, particularly against Gram-negative bacteria, while 6b, 6 g, and 6 h demonstrated strong antifungal effects. Molecular docking, molecular dynamics simulations, and MM-GBSA calculations highlighted strong binding interactions and stable conformations of the active compounds within binding pocket of the FabZ enzyme. The ADMET analyses further indicated that these compounds possess favorable drug-like properties. CONCLUSION: The synthesized 8-hydroxyquinoline-4-thiazolidinone hybrids exhibit strong potential as broad-spectrum antimicrobial agents and merit further investigation as drug candidates.