In this study, high-protein nutrition bars (HPNBs) were prepared using sodium caseinate and either fructose or maltitol as raw materials. The effects of the incorporation of hydroxypropyl methylcellulose (HPMC) on the hardness and physicochemical changes of HPNBs during storage were evaluated. Both HPNB systems containing HPMC exhibited significantly lower hardness than the control HPNBs (no HPMC) during storage, and the change in hardness was dependent on the concentration of HPMC added. The incorporation of 2% HPMC reduced the hardness of the fructose-containing and maltitol-contianing HPNBs by 44.83% and 27.89%, respectively, after 35 days of storage. The addition of HPMC inhibited Maillard reactions within the fructose-containing HPNBs, which exhibited little changes in the total color and composition of free amines. HPMC also significantly mitigated the increase in the insoluble protein content and the transformation of β-turn to β-sheet in proteins that were observed in both HPNB systems during storage. Scanning electron microscopy also confirmed that the texture of the HPNB containing HPMC changed less during storage compared to the controls. These results indicated that HPMC could be used as an inhibitor to reduce the extent of Maillard reactions and protein aggregation during food storage.