A new class of biodegradable and biocompatible poly(butylene 1,4-cyclohexanedicarboxylate) based random copolymers are proposed for biomedical applications. The introduction of ether-oxygen containing BDG sequences along the PBCE macromolecular chain is expected to remarkably improve chain flexibility and surface hydrophilicity due to the presence of highly electronegative oxygen atoms. P(BCExBDGy) copolymers were synthesized by polycondensation. The homopolymer PBCE and three copolymers, namely (P(BCE70BDG30), P(BCE55BDG45) and P(BCE40BDG60)) were characterized from the molecular, thermal, structural and mechanical point of view. Hydrolytic degradation studies in the presence and absence of hog-pancreas lipase were performed under physiological conditions. To evaluate the diffusion profile of small molecules through the polymer matrix, the release behaviour of fluorescein isothiocyanate (FITC) was investigated. For biocompatibility studies, cell adhesion and proliferation of murine fibroblast (L929) and endocrine pancreatic (INS-1) cells were performed on each polymeric film. Results showed that solid-state properties can be tailored by simply varying copolymers' composition. Crystallinity degree and hydrophobicity significantly decreased with the increase of BDG co-unit mol%. Moreover, mechanical properties and biodegradability of PBCE, both depending on crystallinity degree, were remarkably improved: P(BCE40BDG60) showed an elastomeric behaviour with εb over 600% and, as regard to biodegradability, after 98days it lost over 60% of its initial weight if incubated in the presence of the pancreatic lipase. Lastly, the newly developed biomaterials resulted not cytotoxic with both types of cells and could be properly tailored for biomedical applications varying the content of BDG co-unit mol%.