A novel lotus seedpod (LSP) like array substrate with tailorable annular nanogaps is reported for surface‐enhanced Raman spectroscopy (SERS). High SERS activity with excellent Raman signal reproducibility is achieved for molecular detection. Finite‐different time‐domain simulation suggests that sub‐10 nm annular nanogaps formed in the LSP array contribute significantly to the electromagnetic field enhancement for SERS measurements. The SERS substrate presents a detection limit as low as 10−12m along with a relative standard deviation as small as 4.1−8.0% in the detection of rhodamine 6G (R6G). Moreover, the linear correlation between Raman intensity and the concentration of R6G indicates the capability of the substrate for quantitative SERS analyses. As a typical example, the SERS substrate is successfully applied to detecting the α‐helical structure of amyloid‐β oligomers at a low concentration of 0.1 × 10−6m, which will be promising for label‐free detection of Alzheimer's disease in its earliest, presymptomatic, and most treatable stages. The as‐fabricated LSP array substrates therefore hold exciting potentials toward SERS‐based chemical and biomedical detections.