Stem cell transplantation has wide application prospects in tissue injury recovery, especially in neurological recovery. However, the low survival rate of stem cells after transplanted to inflammatory lesions seriously limits their therapeutic effect. Here, we reported that the bioactive black phosphorus nanosheets (BPNs) can effectively improve the antioxidant capacity of stem cells and protect stem cells from oxidative stress-induced cell damage. The antioxidant activity of BPNs was found in different types of stem cells, mainly due to the significantly upregulated nuclear factor erythroid 2-like 2 (Nrf2)-dependent antioxidant pathways by BPNs. In addition, compared with natural neural progenitor cells (NPCs), BP-treated NPCs could protect neurons from oxidative damage more effectively in vitro. Further in vivo transplantation results also demonstrated that BP-treated NPCs could significantly increase the survival rate and effectively inhibit lipid peroxidation, inflammatory response and neuronal apoptosis in stroke rats. Our study reveals a novel biological effect of BPNs on stem cells, which expands the biomedical application of BPNs and opens a new way to increase the therapeutic effects of stem cell.