Instructive tissue engineering biomaterials provide a vascular niche and protect oxidative stress in injured tissue. In this study, we exploited bioinspired bacteriophage nanofibers, previously recognized by their biochemical and structural cues inducing angiogenesis, as an antioxidant tissue engineering material. We demonstrated that topological cues of Arg-Gly-Asp (RGD)-engineered bacteriophage nanofibers provide angiogenic niches and cytoprotective functions against cellular oxidative stress with increased expression of antioxidant enzymes heme oxygenase-1 (HO-1) and NAD(P)H-quinone oxidoreductase 1 (NQO1) via the extracellular-signal-regulated kinase (ERK)–nuclear factor erythroid 2–related factor2 (Nrf2)-mediated signaling pathway, where a high density of RGD cues on the phage body support efficient interaction of cells with phage cues. These bioinspired RGD-engineered bacteriophage nanofibers can serve as a novel therapeutic platform for curing ischemic diseases.