Gold nanorods (AuNRs) with a controllable aspect ratio are anchored on the surface of delaminated nano mica platelets (NMPs) in the presence of a cationic interfacial activator and protective agent enabling the positive charging of the AuNR and nanohybrid surfaces. The high anionic charge and specific surface area of NMPs stabilize AuNR growth and benefit the adsorption of anionic analytes. The nanohybrids (AuNRs/NMPs) exhibit a 3D hotspot effect due to self-assembly and feature regularly arranged AuNRs, thus enabling Raman signal enhancement and sensitive (limit of detection (LOD) = 10 m, Raman enhancement factor (EF) = 2.0 × 10) and reproducible (relative standard deviation (RSD) = 8.82%) adenine detection based on surface-enhanced Raman scattering (SERS). The further incorporation of ZnO quantum dots (QDs) affords nanohybrids (AuNRs/NMPs/ZnO QDs) that exhibit electromagnetic and chemical signal enhancement mechanisms and enable more sensitive and reproducible adenine detection (LOD = 10 m, EF = 1.6 × 10, RSD = 7.66%). AuNRs/NMPs/ZnO QDs are subsequently used for the selective and sensitive SERS-based detection of Helicobacter pylori (LOD = 90 CFU mL). Thus, this work paves the way for the noninvasive, nonfluorescent labeling, rapid, sensitive, selective, and reproducible detection of H. pylori.