In this study, biodegradable and antibacterial poly(azomethine-urethane) (PAMU)- and chitosan (CS)-based hydrogels have been prepared for controlled drug delivery applications. Structural and morphological characterizations of the hydrogels were performed via Fourier transform-infrared and scanning electron microscopy analyses. Thermal stability, hydrophilicity, swelling, mechanical, biodegradation, protein absorption properties, and drug delivery application of PAMU- and CS-based hydrogels were also investigated. The swelling performance of the hydrogels was studied in acidic, neutral, and alkaline media. Swelling results showed that the hydrogels have higher swelling capacity in acidic and alkaline media than neutral medium. Biodegradation experiments of the hydrogels were also studied via hydrolytic and enzymatic experiments. The drug release property of the hydrogel was carried out using 5-fluoro uracil (5-FU), and 5-FU release capacity of the hydrogels was found in the range from 40.10% to 58.40% after 3 days.