The objective of this study was to improve the biomechanical performance of titanium (Ti) using a biocompatible electrospun nanofiber matrix. The study is based on the hypothesis that coating a Ti surface with a nanofiber matrix (NFM) made of collagen (CG) and polycaprolactone (PCL) electrospun nanofibers could increase the mechanical fixation of Ti/bone by improving the surface and cytocompatibility properties of Ti. This study prepared Ti samples with and without CG-PCL NFM coatings. This study determined the in vitro effects of each group of Ti samples on the surface topography and cytocompatibility (osteoblast cell adhesion, proliferation, mineralization and protein adsorption) properties. This study also determined in vivo interface shear strength and bone volume fraction of each group of Ti samples with bone using a rabbit model. This study found that the CG-PCL NFM coating on Ti improved the surface roughness, osteoblast cell adhesion, proliferation, mineralization and protein adsorption properties of Ti. In vivo studies found that interface shear strength of CG-PCL NFM-coated Ti/bone samples was significantly higher compared to those values of control Ti/bone samples (p value < 0.05) due to an increase in the amount of growth of the connective tissue joining the Ti implant. Therefore, the developed CG-PCL NFM coating technique should further be investigated for its potential in clinical applications.