Sweet mogrosides are not only the primary bioactive ingredient inSiraitia grosvenoriifruits that exhibit anti-tussive properties and expectorate phlegm, but they are also responsible for the fruit’s sweetness. Increasing the content or proportion of sweet mogrosides inSiraitia grosvenoriifruits is significant for improving their quality and industrial production. Post-ripening is an essential step in the post-harvest processing ofSiraitia grosvenoriifruits, but the underlying mechanism and condition of post-ripening onSiraitia grosvenoriiquality improvement need to be studied systematically. Therefore, this study analyzed the mogroside metabolism inSiraitia grosvenoriifruits under different post-ripening conditions. We further examined the catalytic activity of glycosyltransferase UGT94-289-3in vitro. The results showed that the post-ripening process of fruits could catalyze the glycosylation of bitter-tasting mogroside IIE and III to form sweet mogrosides containing four to six glucose units. After ripening at 35 °C for two weeks, the content of mogroside V changed significantly, with a maximum increase of 80%, while the increase in mogroside VI was over twice its initial amount. Furthermore, under the suitable catalytic condition, UGT94-289-3 could efficiently convert the mogrosides with less than three glucose units into structurally diverse sweet mogrosides, i.e., with mogroside III as the substrate, 95% of it can converted into sweet mogrosides. These findings suggest that controlling the temperature and related catalytic conditions may activate UGT94-289-3 and promote the accumulation of sweet mogrosides. This study provides an effective method for improving the quality ofSiraitia grosvenoriifruits and the accumulation of sweet mogrosides, as well as a new economical, green, and efficient method for producing sweet mogrosides.