Nisin is a natural bacteriocin that exhibits good antibacterial activity against Gram-positive bacteria. It has good solubility, stability, and activity under acidic conditions, but it becomes less soluble, stable, and active when the solution pH exceeds 6.0, which severely restricted the industrial application range of nisin as antibacterial agent. In this study, we investigated the potential of complexing nisin with a cyclodextrin carboxylate, succinic acid-β-cyclodextrin (SACD), to overcome the disadvantages. Strong hydrogen bonding was shown between the nisin and SACD, promoting the formation of nisin-SACD complexes. These complexes exhibited good solubility under neutral and alkaline conditions, and good stability after being held at high pH values during processing with high-steam sterilization. Moreover, the nisin-SACD complexes displayed significantly improved antibacterial activity against model Gram-positive bacteria (S. aureus). This study shows that complexation can improve the efficacy of nisin under neutral and alkaline situations, which may greatly broaden its application range in food, medical, and other industries.