Presently, the anticancer activity with higher performance and lesser side effects remains a greater challenge in the scientific and medicinal research. We aim to fabricate natural ingredient or extract (curcumin/neem) loaded polycaprolactone (PCL) nanofibres. The fabricated nanofibre were characterised by Fourier transform infrared (FTIR) spectroscopy, Scanning electron microscopy (SEM) and Static water contact angle measurement to investigate the chemical nature, surface morphology and hydrophilicity of the polymer surface. The PCL nanofibre diameter decreases considerably by the addition of neem extract than the addition of curcumin and curcumin/neem to PCL nanofibre, which is confirmed by SEM analysis. The fabricated nanofibres anti-cancer activity and cytotoxic efficiency were conducted on A431 cancer cells and HaCaT skin cells. PCL/Cur/Neem nanofibre showed higher anticancer activity and the PCL and PCL/Cur/Neem nanofibre showed lower cytotoxic activity against HaCaT skin cells.