Reactive oxygen species (ROS)-responsive materials have attracted considerable attention for developing smart therapeutic systems capable of targeted drug delivery under oxidative stress. In the present study, two long-chain tertiary amino alcohols, N-Dodecyl-N-methylaminoethanol and N-Hexadecyl-N-methylaminoethanol, were synthesized and investigated as ROS-responsive organic molecules for incorporation into chitosan-based hydrogels. The chemical stability of the synthesized compounds was evaluated under physiological and mildly acidic conditions in the presence of hydrogen peroxide using ATR-FTIR spectroscopy. Both compounds exhibited characteristic absorption bands corresponding to tertiary amino alcohols, and only minor spectral variations were observed following oxidative treatment, primarily within the O–H stretching and fingerprint regions. Importantly, no carbonyl absorption bands indicative of oxidative degradation were detected within the sensitivity of ATR-FTIR, suggesting that the amino-alcohol backbone remained chemically intact under the conditions tested; as ATR-FTIR alone cannot definitively establish antioxidant or radical-scavenging activity, this finding is interpreted as evidence of chemical robustness rather than a proven antioxidant effect. The synthesized amine derivatives were subsequently incorporated into chitosan/β-glycerophosphate hydrogels, and FTIR analysis confirmed successful formulation without disrupting the polymeric network. The observed spectral changes suggest reversible protonation or limited oxidation of the tertiary amine functionality while preserving the long alkyl chains. The enhanced stability of the hexadecyl analogue further indicates the influence of alkyl chain length on oxidative resistance. These findings demonstrate that long-chain tertiary amino alcohols are promising organic building blocks for the design of ROS-responsive biomaterials and provide a foundation for developing smart hydrogel systems for controlled therapeutic delivery.

Periodontitis is a chronic, multifactorial inflammatory disease driven by microbial dysbiosis, oxidative stress, and dysregulated host immune responses, resulting in progressive destruction of periodontal tissues and, ultimately, tooth loss. Traditional treatments, including scaling and root planing and systemic antibiotics, have limitations due to incomplete bacterial elimination, poor site specificity, short drug retention, systemic side effects, and limited regenerative support. Recently, chitosan (CS)‐based hydrogels have emerged as promising biomaterials for localized periodontal treatment owing to their biocompatibility, biodegradability, mucoadhesive nature, and ease of chemical modification. This review critically discusses recent developments in CS‐based hydrogel systems functionalized with antibiotics, phytochemicals, anti‐inflammatory agents, nanoparticles, regenerative molecules, and stimuli‐responsive materials for the management of periodontitis. It primarily focuses on periodontal pathophysiology, therapeutic strategies, and drug‐polymer interactions that affect its performance. Furthermore, it highlights emerging smart hydrogel systems that respond to pH, reactive oxygen species, temperature, and enzymatic activity within the periodontal microenvironment for controlled, targeted drug delivery. Future perspectives involve the development of multi‐stimuli‐responsive, microbiome‐preserving, self‐healing, and personalized hydrogel platforms capable of sequential drug delivery and periodontal regeneration. On the whole, this review bridges the gap between materials chemistry and clinical applicability, providing insights into design of next‐generation CS‐based hydrogels for targeted periodontal therapy.