To achieve ultrasensitive detection of trace targets through solution-based surface-enhanced Raman spectroscopy (SERS), direct adsorption of the target molecules on a SERS-active surface is vital. In this work, cetyltrimethylammonium bromide (CTAB)-capped gold nano-bipyramids (Au BPs) with different aspect ratios (ARs) are prepared and the surface is successfully modified by a simple ligand exchange method. Cysteamine-capped gold nano-bipyramids (cyst-Au BPs) are obtained by means of replacement of CTAB by cysteamine using Au-S covalent bonding and applied in the solution-based SERS detection of different pigment molecules, which always have weak affinity to the gold surface. The hydrogen bonding between the pigment molecule and cysteamine causes the aggregation of Au BPs to generate local electromagnetic field enhancement. The influence of the AR and concentration of Au BPs on SERS properties is investigated. The SERS detection of weak-affinity molecules to an extremely low limit shows that the cyst-Au BPs are highly sensitive compared to CTAB-capped Au BPs. The limit of detection (LOD) of allura red as low as 0.1 ppb and that of sunset yellow as low as 1 ppb show that the proposed strategy has many advantages due to its simplicity and fast and rapid detection for the sensitivity analysis of weak-affinity molecules.