Polypeptide-derived copolymers have widely been exploited for drug/gene delivery due to their pendant functional groups and non-toxic degradation products. However, fabrication of polypeptide-based scaffolds for tissue engineering has seldom been reported. In this study, foamy poly(N ε -benzyl formateoxycarbonyl-L-Lysine) (PZL) and poly(N ε -benzyl formateoxycarbonyl-L-lysine-co-L-phenylalanine) (PZLP) scaffolds were successfully prepared by a combination of ring-opening polymerization of α-amino acid N-carboxyanhydride and negative porous NaCl templating approach. The physicochemical properties of these scaffolds including glass transition temperature, contact angle, compression modulus and degradation behavior were characterized. Both in vitro and in vivo biocompatibility of the scaffolds were evaluated by MC3T3-E1 cell culture and SD subcutaneous model, respectively. The results from live-dead staining, MTT and ALP activity assays indicated that PZL scaffolds were more conducive to the adhesion, proliferation and osteoblastic differentiation of MC3T3-E1 cells compared to PZLP scaffolds in the initial culture period due to their specific surface properties. While porous structure rather than surface properties of scaffolds played a decisive role in the later stage of cell culture. The results of in vivo studies including H&E, Masson's trichrome and CD34 staining further demonstrated that PZL scaffolds supported the ingrowth of microvessels than PZLP scaffolds due to their surface property difference. Collectively, PZL scaffolds displayed good biocompatibility and could be a promising candidate for tissue engineering application.