Trichosanthis Fructus (TrF) is an edible medicinal fruit with a sweet taste and pleasant flavor. In this study, different concentrations of TrF were added into the media to brew Monascus rice wine using a pure culture method, and the physicochemical properties, volatile compounds, antioxidant activity, and sensory quality of the brewed samples were characterized. In addition, the effect of TrF on the growth and metabolism of Monascus purpureus and Saccharomyces cerevisiae was investigated. The results show that addition of TrF reduces the growth and metabolism of M. purpureus and S. cerevisiae in a dose-dependent manner, but also enriches the flavor components, in addition to increasing the total phenolic and flavonoid contents, and antioxidant activity of rice wine. Combined with the results of sensory evaluation, we find that 15% TrF is optimal for improving the flavor of Monascus rice wine. The results from this study can serve as a basis for improving the quality and flavor of rice wine brewed using pure strain culture.