Poly(ε-caprolactone) (PCL) is commonly used in devices for tissue reconstruction due to its biocompatibility and suitable mechanical properties. However, its high crystallinity and hydrophobicity do not favor cell adhesion and difficult polymer bioresorption. To improve these characteristics, the development of engineered scaffolds for tissue regeneration, based on poly(globalide-co-ε-caprolactone) (PGlCL) covalently bonded with N-acetylcysteine (PGlCL-NAC) was proposed. The scaffolds were obtained from polymer blends of PCL and PGlCL-NAC, using the electrospinning technique. The use of PGlCL-NAC allowed for the modification of the physical and chemical properties of PCL electrospun scaffolds, including an expressive reduction in the fiber's diameter, hydrophobicity, and crystallinity. All electrospun scaffolds showed no cytotoxicity against fibroblasts (McCoy cells). In vitro biocompatibility assays showed that all tested scaffolds provided high cell viability and proliferation in short-term (NRU, MTT, and nuclear morphology assays) and long-term (clonogenic assay) assays. Nevertheless, PGlCL-NAC based scaffolds have favored the survival and proliferation of the cells in comparison to PCL scaffolds. Cell adhesion on the scaffolds assessed by electronic microscopy images confirmed this behavior. These results suggest that the incorporation of PGlCL-NAC in scaffolds for tissue regeneration could be a promising strategy to improve cell−surface interactions and contribute to the development of more efficiently engineered biomedical devices.