A novel approach has been successfully developed to synthesize Pd@Au core/shell nanosheets by using lemon extract as a biological reducing agent and microwave heating. This approach is suggested to be an eco-friendly, rapid and simple method for the synthesis of Pd@Au core/shell nanosheets. The Au shells that covered the Pd nanosheet surfaces were formed at 80 W in microwave for 20 min. The prepared Pd@Au core/shell nanosheets were characterized by UV–vis spectrophotometry, X-Ray diffraction, transmission electron microscopy, energy dispersive X-ray, energy dispersive X-ray elemental-mapping and energy dispersive X-ray line profile. A highly self-assemblage surface-enhanced Raman scattering methodology was developed by applying Pd@Au core/shell nanosheets for trace fluorescent dye detection. The highest R6G signal was attained with an Au layer of about 3 nm thickness. The results show that the SERS technique is able to detect trace fluorescent dye within a wide concentration range from 10−8 M to 10−17 M, with an extremely low limit of detection of 10−17 M. The study offers a low-cost route to the fabrication of sensing devices capable of use for monitoring cancer progression in natural matrices such as blood.