Dental implant prostheses cannot preclude a correct and stable implant osseointegration, which is still a challenge and greatly depends on biomaterial-cell interface. Titanium (Ti) coating using polyelectrolyte poly-L-lysine (PLL) may represent an interesting and simple approach, to provide a charged surface net able to improve cell adherence. However, in vitro and in vivo effects of Ti coated with PLL have been poorly investigated. The aims of the present study are (1) to obtain and characterize, chemically and physically, Ti disks coated with PLL (TiPLL); (2) to perform in vitro studies on osteoblast cell lines' cytocompatibility and functionality (alkaline phosphatase [ALP] activity, calcium deposition, proinflammatory interleukin 6 production); (3) to obtain in vivo evidence of osseointegration, using a sheep animal model. XPS, AFM, and contact-angle analyses demonstrated that the Ti disk was successfully covered with PLL, providing higher hydrophilicity to the Ti disk. No cellular toxicity, enhanced calcium deposition, and a decreased tendency toward interleukin-6 production were observed in the osteoblast seeded onto TiPLL. In vivo experiments showed cortical bone microhardness at 3 months significantly improved in the presence of the PLL coating. PLL coating on Ti implants seemed to safely enhance calcium deposition and implant early osseointegration in animals, suggesting promising evidence to optimize the surface properties of dental implants.