Safe and efficient provision of electrical stimulation (ES) for nerve repair and regeneration is a problem that needs to be addressed. In this study, a silk fibroin/poly(vinylidene fluoride-co-hexafluoropropylene)/Ti3C2Tx (SF/PVDF-HFP/MXene) composite scaffold with piezoelectricity was developed by electrospinning technology. MXene was loaded to the scaffold to enhance the piezoelectric properties (Output voltage reaches up to 100 mV), mechanical properties, and antibacterial activity. Cell experiments demonstrated piezoelectric stimulation under external ultrasonication for promoting the growth and proliferation of Schwann cells (SCs) cultured on this electrospun scaffold. Further in vivo study with rat sciatic nerve injury model revealed that the SF/PVDF-HFP/MXene nerve conduit could induce the proliferation of SCs, enhance the elongation of axon, and promote axonal myelination. Under the piezoelectric effect of this nerve scaffold, the rats with regenerative nerve exhibited a favorable recovery effect of motor and sensory function, indicating a safe and feasible method of using this SF/PVDF-HFP/MXene piezoelectric scaffold for ES provision in vivo.