The objective of this study was to formulate and evaluate metronidazole tableted microspheres aimed at targeted colonic delivery, enhancing the therapeutic efficacy and reducing systemic side effects. Metronidazole, an antimicrobial agent widely used in the treatment of colonic infections and inflammatory bowel diseases, benefits significantly from site-specific delivery. Microspheres were prepared using an emulsion-solvent evaporation method, incorporating metronidazole into a biodegradable polymer matrix of Eudragit S100, designed to release the drug specifically in the colonic environment.Characterization of the microspheres included particle size analysis, surface morphology via scanning electron microscopy (SEM), encapsulation efficiency, and in-vitro drug release studies. The particle size of the microspheres ranged between 50-150 μm with a smooth surface, ensuring uniform distribution. Encapsulation efficiency was determined to be 85%, indicating effective drug loading within the microspheres. In-vitro release studies in simulated gastrointestinal fluids showed minimal drug release in the acidic environment of the stomach and the neutral pH of the small intestine. However, a significant release was observed in the colonic pH environment, confirming the targeted delivery potential of the formulation.Tableting of the microspheres was performed using direct compression with suitable excipients, maintaining the integrity of the microspheres. The tableted microspheres demonstrated acceptable hardness, friability, and disintegration time, aligning with pharmacopeial standards.In conclusion, the formulated metronidazole tableted microspheres exhibit promising characteristics for colonic delivery, providing a potential approach for enhancing the treatment of colonic diseases while minimizing systemic exposure and side effects. Further in-vivo studies are warranted to corroborate these findings and optimize the formulation for clinical application.