Hydrogels are ideal biomaterials owing to their unique network structure that facilitates considerable hydrophilicity and biocompatibility. At the same time, hydrogels also possess soft physical properties when combined with living tissue. In this study, metformin hydrogen chloride (metformin HCl)-loaded stimuli-responsive poly(N-isopropylacrylamide) (pNIPAAm) -chitosanpolyvinyl alcohol (PVA) hydrogels were synthesized through a freezing and thawing procedure and subsequently subjected to gamma irradiation at room temperature. The gel content and the water absorption capacity of the synthesized hydrogels were analyzed. The polymer interaction in the matrix was observed by Fourier transform infrared spectroscopy, and the release of metformin HCl was studied in different pHs and temperatures. The hydrogels had 85% of the gel content and 373% of the water absorption capacity after 24 h of water immersion. The metformin HCl-loaded (pNIPAAm-chitosan-PVA) hydrogels demonstrated a sustained drug release profile over 7 h. The drug release exhibited pH-dependent and temperature-dependent behavior. The developed hydrogels showed good metformin HCl release ability at pH 3 and pH 6.86 at the temperature of 37 o C. The results showed that pNIPAAm-chitosan-PVA hydrogels could be employed for controlled drug release of metformin HCl.