Low-Temperature Vacuum Drying (LTVD) could be considered an alternative to conventional food drying methods at high temperature in preserving bioactive compounds from foods. Thereby, the aim of this work was to evaluate the antioxidant and antimicrobial potential of papaya (Vasconcellea pubescens) pulp after LTVD compared to other drying methods including freeze-drying (FD), vacuum-drying (VD), convective-drying (CD) and infrared-drying (IRD). The drying rate was significantly influenced by the drying methods and temperatures. Compared with FD, LTVD resulted in a 52% decrease in drying time. Both disk-diffusion and minimal inhibitory concentration (MIC) assays showed increased antimicrobial activity for extracts prepared with dehydrated papaya. The lowest MIC (15.6 mg mL−1) was found against Bacillus cereus for extracts prepared with VD, CD and IRD papaya. All antioxidant compounds tested decreased after dehydration; however, a strong correlation was observed between DPPH and the antimicrobial activity against E. coli and B. cereus for all extracts prepared with dried papaya pulp. Therefore, dried papaya extracts can be good candidates for the development of natural preservatives regardless of the drying method used.Industrial relevance: Low-temperature vacuum dehydration (LTVD) is a novel technology that was initially developed for the drying of sensitive food ingredients. However, it is unknown if this technique can protect the heat sensitive antimicrobial compounds of fruits.