The investigation of plasmonic chirality is a profound and intriguing topic, and the distinctive morphology of intrinsically chiral nanoparticles has prompted significant interest in the structure−activity relationship between particle morphology and chirality. In this work, the anisotropic etching of chiral helical gold nanorods (HGNRs) by a cetyltrimethylammonium bromide (CTAB)−HAuCl 4 complex was observed with an interesting bidirectional variation of intrinsic chirality that initially enhanced and subsequently weakened, which was related with the diversity in CTAB distribution. In addition, an ultrasensitive and convenient sensing platform for acetylcholinesterase was developed based on the circular dichroism signal recovery of HGNRs caused by the dual inhibition of HGNR etching. The distinctive etching process and mechanism of chiral nanoparticles offer new insights into understanding the structural features and biochemical applications of the plasmonic intrinsic chirality, which could be applied to the acquisition of chiral nanoparticles and sensitive detection platform based on chiral signal changes.