Nanogap-rich 3D plasmonic nanostructures provide enhanced molecular Raman fingerprints in a nondestructive and label-free manner. However, the molecular detection of small target molecules in complex fluids is challenging due to nonspecific protein adsorption, which prevents access of the target molecules. Therefore, the molecular detection for complex mixtures usually requires a tedious and time-consuming pretreatment of samples. Herein, we report the encapsulation of 3D plasmonic nanostructures with an ultrathin hydrogel skin for the rapid and direct detection of small molecules in complex mixtures. To demonstrate the proof of concept, we directly detect pesticide dissolved in milk without pretreatment. This detection is enabled by the selective permeation of target molecules into the 3D mesh of the hydrogel skin and the adsorption onto plasmonic hotspots, accompanied by the rejection of large adhesive proteins and colloids. The high sensitivity of nanogap-rich plasmonic nanostructures in a conjunction with the molecular selection of the hydrogel skin enables the fast and reliable detection of tricyclazole in whole milk with a limit of detection as low as 10 ppb within 1 h. We believe that this plasmonic platform is highly adaptable for in situ and on-site detection of small molecules in various complex mixtures including foods, biological fluids, and environmental fluids.