Enhanced two-photon fluorescence (TPF) spectroscopy with novel high-finesse resonant polymeric grating waveguide structures (GWSs) is presented. Under resonant conditions the field enhancement at the surface of a GWS can be exploited for TPF spectroscopy without the need for highly focused laser excitation light. We compare the TPF obtained by placing a drop of tetramethylrhodamine (TMR) on top of a GWS with that obtained with TMR on top of a glass substrate. Our procedure and results indicate that the detection of TPF can be improved by a factor of 10 with resonant GWSs.