Polydopamine (PDA) depositions, inspired by mussel foot adhesive proteins, represent a versatile method for preparing separation membranes. However, PDA-based nanofiltration membranes are limited by the long preparation time and moderate flux. This work modulated PDA deposition processes with a spiro-piperazine (SPIP) molecule containing two secondary amine groups and a quaternary ammonium salt. The SPIP could be covalently inserted into PDA coating structures via Michael addition reaction to accelerate the deposition process of PDA and reduce its aggregation. In addition, the rigid and spiro configuration of SPIP molecules provides higher fractional free volume and leads to looser and more uniform structures in the PDA coating. As such, water permeance of PDA/SPIP membranes is 73 L m−2 h−1 bar−1, 4.6 times improved compared with PDA control membranes, while the dye rejection (>99% for Congo red) is maintained high. These results demonstrate that SPIP is an effective molecule for the structure and performance engineering of mussel-inspired PDA nanofiltration membranes.