In this study, the heat pump drying characteristics of the raw material, fresh Luffa acutangula (Linn.) Roxb., was studied. On the basis of the results of single-factor experiments, Box-Behnken Design (BBD) was used to design and optimize the experimental conditions for the studies on the effects of different slice thickness, drying air speed and drying temperature on drying time, rehydration ratio and polyphenol content. Moreover, the predictive model of the regression equation was obtained using the Design-Expert software, and the heat pump drying process variables were optimized by response surface methodology. Polyphenols were extracted with acetone from the heat pump dried Luffa acutangula (Linn.) Roxb., and the antioxidant activity of polyphenols from Luffa acutangula (Linn.) Roxb. was evaluated as DPPH free radical scavenging activity. The results showed that the optimal heat pump drying conditions were: slice thickness 5.22 mm, drying air speed 1.62 m/s, drying temperature 62.6 ℃. It was predicted that the drying time, rehydration ratio and polyphenol content were 2.56 h, 16.1, 1.89 mg/g, respectively, under the optimal drying conditions. Considering the actual operational feasibility, the drying process variables were adjusted to: slice thickness 5 mm, drying air speed 1.6 m/s, drying temperature 63 ℃. Under such conditions, the drying time, rehydration ratio and polyphenol content were 2.24 h, 16.05, 1.88 mg/g, which were in good agreement with the predicted values. The antioxidant activity was positively correlated with the polyphenol content within a certain range. When the mass concentration increased to 0.15 mg/mL, the DPPH free radical scavenging rate reached 78.13%. The Luffa acutangula (Linn.) Roxb. dried by the heat pump showed good rehydration behavior and good sensory quality with its polyphenols exhibiting a certain ability to scavenge DPPH free radicals.