The present study conceived a novel series of thiazole, indole and thiazolidine derivatives 4-6 have been developed and characterized by IR, Proton Nuclear Magnetic Resonance (1H-NMR), Carbon-13 Nuclear Magnetic Resonance (13C-NMR) and mass spectral data and elemental analysis and evaluated for in vitro antimicrobial activity against bacterial strains such as, Escherichia coli (MTCC-723), Staphylococcus aureus (ATCC-29513), Klebsiella pneumonia (NCTC-13368), Pseudomonas aeruginosa (MTCC-1688) and the fungal strains such as Aspergillus oryzae (MTCC-3567T), Aspergillus niger (MTCC-281), Aspergillus flavus (MTCC-1973), Aspergillus terreus (MTCC-1782). A. niger were carried out by broth micro dilution method (NCCLS., 2002) in DMF concentration at 500, 250, 125 and 62.5 μg/ml. Gentamycin and fluconazole was used as reference standards for antibacterial and antifungal activity, respectively. The newly designed and synthesized compounds were evaluated for their antimicrobial activity. The final results revealed that compounds 4b, 5b and 6b were exhibited potent antimicrobial activity when compared to the standard drugs.