Sulfur dioxide (SO2) is widely used in the fruit wine industry due to its antioxidant and antibacterial properties. However, concerns about its potential harmful effects on human health have prompted researchers to seek alternative treatments. In this study, nisin, a natural nontoxic polypeptide, was introduced as a preservative during dateplum persimmon (Diospyros lotus L.) winemaking. The ideal fermentation conditions were determined through response surface methodology optimization: a nisin content of 0.21 g/L, a yeast concentration of 0.22%, and an initial sugar content of 255 g/L. Enological parameters, microbiological analysis, sensory evaluation, and volatile component information were compared between dateplum persimmon wines made with nisin and those made with SO2 both before and after three months of aging. Notably, the major components were consistent across all the samples, with 3-methylbutanol, ethyl caprylate, 2-methylbutanol, and phenethyl alcohol imparting apple brandy, honey, and rose aromas to the fruit wines. Overall, these results suggest that nisin can serve as an effective and acceptable alternative to SO2, demonstrating satisfactory antibacterial properties without adverse effects on wine quality. This study marks the first exploration of the potential use of nisin in the production of dateplum persimmon wine, offering a promising avenue for the replacement of SO2 in fruit wine processing.