Tissue engineering involves a multifunctional temporary matrix which regulates tissue regeneration through controlled drug release against infections. A nanofibrous core-sheath structured scaffold comprising a tetracycline-loaded alginate/soy protein isolate (TCH-Alg/SPI) as a core and polycaprolactone (PCL) as a sheath was developed using co-axial electrospinning. Coverage of hydrophobic PCL on TCH-Alg/SPI fibers enhanced their structural stability in aqueous solutions as unsheathed fibers rapidly decomposed and provided fast drug release. Core-sheath fibers exhibited an initial burst release at ~49 % after 6 h of immersion in phosphate-buffered saline (PBS) solution and the sustain release reached ~80 % of total loaded drug on day 14. Release characteristics of TCH-Alg/SPI fibers without PCL covering showed immediate drug release within 48 h. Core-sheath fibers investigated by disk diffusion exhibited antibacterial properties against Staphylococcus aureus and Escherichia coli. The non-toxicity of core-sheath fibers was confirmed by an indirect cytotoxicity test using human dermal fibroblasts which showed compatibility and high cell viability of up to 100 % in treated cells. TCH-Alg/SPI-PCL core-sheath fibers show promise as tissue engineering scaffolds which can act as temporary templates for tissue regeneration and exhibit antibiotic release functions against infections caused by pathogenic microorganisms.