The uniform dispersion of the nano fillers without agglomeration in a polymeric matrix is widely adapted for the purpose of mechanical properties enhancement. In the context to biomedical applications, the type and amount of nanoparticles can potentially influence the biocompatibility. In order to address these issues, High Density Polyethylene (HDPE) based composites reinforced with graphene oxide (GO) were prepared by melt mixing followed by compression moulding. In an attempt to tailor the dispersion and to improve the interfacial adhesion, polyethylene (PE) was immobilized onto GO sheets by nucleophilic addition-elimination reaction. A good combination of yield strength (ca. 20 MPa), elastic modulus (ca. 600 MPa) and an outstanding elongation at failure (ca. 70 %) were recorded with 3 wt % polyethylene grafted graphene oxide (PE-g-GO) reinforced HDPE composites. Considering the relevance of protein adsorption as a biophysical precursor to cell adhesion, the protein adsorption isotherms of bovine serum albumin (BSA) were determined to realize three times higher equilibrium constant (Keq) for PE-g-GO reinforced HDPE composites as compared to GO reinforced composites. In order to assess the cytocompatibility, osteoblast cells (MC3T3) were grown on HDPE/GO and HDPE/PE-g-GO composites, in vitro. The statistically significant increase in metabolically active cell was observed, irrespective of the substrate composition. Such observation indicated that HDPE with GO or PE-g-GO addition (upto 3 wt %) can be used as cell growth substrate. The extensive proliferation of cells with oriented growth pattern also supported the fact that tailored GO addition can support cellular functionality, in vitro. Taken together, the experimental results suggest that the PE-g-GO in HDPE can effectively be utilized to enhance both mechanical and cytocompatibility properties and can further be explored for potential biomedical applications.