Lignin polymerization has been considered as an effective approach for lignin valorization. Herein we report the synthesis of a series of new lignin-based copolymers (lignin poly(epsilon-caprolactone-co-lactide), lignin PCLLA) via solvent-free ring-opening polymerization. Lignin PCLLA copolymers with tunable molecular weights (10 to 16 kDa) and glass transition temperatures(-40 to 40 degrees C) were obtained. Such copolymers were engineered into ultrafine nanofibers by blending with polyesters (polycaprolactone, PCL and poly(L-lactic acid), PLLA) via electrospinning. Both PCL/lignin PCLLA and PLLA/lignin PCLLA nanofibers displayed uniform and beadless nanofibrous morphology. The size (diameters ranging from 300 to 500 nm) and tensile tests of the obtained nanofibers indicated that the lignin copolymers are miscible with the polyester matrices and can significantly improve the mechanical properties of the nanofibers. Moreover, good antioxidant activity and biocompatibility of the lignin nanofibers were demonstrated in vitro, certifying the great potential of lignin PCLLA copolymers and nanofibers for biomedical or healthcare applications.