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Porous metal scaffolds play an important role in the orthopedic field, due to their wide applications in prostheses implantation. Some previous studies showed that the scaffolds with trabecular bone structure reconstructed via computed tomography had satisfactory biocompatibility. However, the reverse modeling scaffolds were inflexible for customized design. Therefore, a top-down designing biomimetic bone scaffold with favorable mechanical performances and cytocompatibility is urgently demanded for orthopedic implants. An emerging additive manufacturing technique, selective laser melting, was employed to fabricate the trabecular-like porous Ti-6Al-4 V scaffolds with varying irregularities (0.05-0.5) and porosities (48.83%–74.28%) designed through a novel Voronoi-Tessellation based method. Micro-computed tomography and scanning electron microscopy were used to characterize the scaffolds' morphology. Quasi-static compression tests were performed to evaluate the scaffolds' mechanical properties. The MG63 cells culture in vitro experiments, including adhesion, proliferation, and differentiation, were conducted to study the cytocompatibility of scaffolds. Compressive tests of scaffolds revealed an apparent elastic modulus range of 1.93–5.24 GPa and an ultimate strength ranging within 44.9–237.5 MPa, which were influenced by irregularity and porosity, and improved by heat treatment. Furthermore, the in vitro assay suggested that the original surface of the SLM-fabricated scaffolds was favorable for osteoblasts adhesion and migration because of micro scale pores and ravines. The trabecular-like porous scaffolds with full irregularity and higher porosity exhibited enhanced cells proliferation and osteoblast differentiation at earlier time, due to their preferable combination of small and large pores with various shapes. This study suggested that selective laser melting-derived Ti-6Al-4 V scaffold with the trabecular-like porous structure designed through Voronoi-Tessellation method, favorable mechanical performance, and good cytocompatibility was a potential biomaterial for orthopedic implants. [ABSTRACT FROM AUTHOR]