Collagen-based biomaterials are widely used, but their relatively rapid biodegradation can limit functional duration. Such collagen constructs are widely used as barrier membranes in guided tissue and bone regeneration, where controlled degradation is essential for maintaining function. Although conventional crosslinking methods extend stability, they may introduce cytotoxicity, alter mechanical behavior, or hinder tissue integration. This study evaluated whether incorporating L-serine, a polar amino acid capable of hydrogen bonding, could modulate collagen structure and slow degradation without chemical crosslinking. L-Serine was selected because its hydroxyl-containing side chain can engage in biocompatible, hydrogen-bond-mediated interactions that offer a mild, non-crosslinking means of stabilizing collagen. Collagen scaffolds, prepared by incorporating L-serine into a collagen hydrogel followed by drying, were produced with 0-40 wt% L-serine and characterized using X-ray diffraction, Fourier-transform infrared spectroscopy, circular dichroism, and scanning electron microscopy. In vivo degradation was assessed in a subcutaneous mouse model comparing unmodified collagen, collagen containing 40 wt% L-serine, and a commercially available bilayer porcine collagen membrane (Bio-Gide<sup>®</sup>, composed of type I and III collagen), with residual area quantified by serial sonography and histological evaluation. Low-to-moderate L-serine incorporation preserved triple-helical features, while 40 wt% led to crystalline domain formation and β-sheet enrichment. L-serine-treated collagen exhibited significantly greater residual area (2.70 ± 1.45 mm<sup>2</sup>) than unmodified collagen (0.37 ± 0.22 mm<sup>2</sup>, <i>p</i> < 0.05), although Bio-Gide<sup>®</sup> remained the most persistent (5.64 ± 2.76 mm<sup>2</sup>). These findings demonstrate that L-serine incorporation can modulate collagen structure and degradation kinetics through a simple, aqueous, and non-crosslinking approach. The results provide preliminary feasibility data supporting amino acid-assisted tuning of collagen resorption properties and justify further evaluation using membrane-specific fabrication and application-relevant testing.