Mefentrifluconazole was the first novel isopropyl alcohol triazole fungicide. Existing research indicated that R-mefentrifluconazole had high activity and low toxicity, presenting potential for monocase application, while limited data existed on its enantioselective dissipation in crops. Here, after confirming the absolute configuration, the enantioselective dissipation and risk assessments of chiral mefentrifluconazole in soybeans, peanuts, tomatoes, grapes, and soil were conducted. The preferential dissipation of R-mefentrifluconazole was verified in soybean plants, soybeans, peanut plants, tomatoes, and grapes. The preferential dissipation of S-mefentrifluconazole was verified in the peanut shells and soil. The stereoisomeric excess variations of mefentrifluconazole in soybean plants, soybean, peanut plants, and peanut shells exceeded 10%, and the enantiomer toxicity and behavior differences should be considered in risk assessments. The dietary risks of acute (0.020–1.250%) and chronic (0.054–18.328%) of mefentrifluconazole in these crops were acceptable. R-Mefentrifluconazole might be recommended for use as a monocase product.