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Snake gourd is a seasonal vegetable with a high water content and medicinal value, but the short harvest period limits the large-scale application of snake gourd. Therefore, the effects of freeze–thaw pretreatment (FT) combined with hot air (HD) on the drying characteristics, active ingredients and bioactivities of snake gourd were investigated. The results showed that FT pretreatment reduced browning and shortened the drying time by 44%; the Page model was the best fit for describing the drying process. The polysaccharide contents (21.70% in alcoholic extract (TG1) and 44.34% in water extract (TG2)) and total phenol contents (1.81% in TG1 and 0.88% in TG2) of snake gourd pretreated by FT-HD were higher than those of snake gourd pretreated by the corresponding HD treatment. The FT pretreatment decreased the molecular weight of snake gourd polysaccharides and increased the molar ratio of glucose. The extracts pretreated by FT-HD showed greater chemical, cellular antioxidant capacity and α-amylase and α-glucosidase inhibition than those pretreated by HD. FT-HD can be recommended for achieving a short drying time and high quality of snake gourd and can be used for the drying of other fruits and vegetables.