Titanium (Ti) and titanium alloy have been widely used in orthopedics. However, the successful application of titanium implants is mainly limited due to implant-associated infections. The implant surface contributes to osseointegration, but also has the risk of accelerating the growth of bacterial colonies, and the implant surfaces infected with bacteria easily form biofilms that are resistant to antibiotics. Biofilm-related implant infections are a disastrous complication of trauma orthopedic surgery and occur when an implant is colonized by bacteria. Surface bio-functionalization has been extensively studied to better realize the inhibition of bacterial proliferation to further optimize the mechanical functions of implants. Recently, the surface bio-functionalization of titanium implants has been presented to improve osseointegration. However, there are still numerous clinical and non-clinical challenges. In this review, these aspects were highlighted to develop surface bio-functionalization strategies for enhancing the clinical application of titanium implants to eliminate implant-associated infections.