Several Salmonella outbreaks linked to black pepper call for effective inactivation processes, because current decontamination methods result in quality deterioration. Radio-frequency (RF) heating provides a rapid heating rate and volumetric heating, resulting in a shorter come-up time. This allows for choosing a high-temperature and short-time combination to achieve the desired inactivation with minimal quality deterioration. The objectives of this study were to evaluate RF heating for inactivation of Salmonella enterica and Enterococcus faecium in black peppercorn and evaluate quality changes of RF-treated black peppercorn. Black peppercorns were inoculated with a five-strain cocktail of Salmonella or E. faecium to attain initial population levels of 6.8 and 7.3 log CFU/g, respectively, and were then adjusted to a moisture content of 12.7% (wet basis) and a water activity of 0.60 at room temperature. A stability test was performed to quantify the microbial reduction during inoculation and equilibration before RF heating inactivation. During RF heating, the cold spot was determined to be at the center on the top surface of the treated sample. In addition to inoculating the entire sample, an inoculated packed sample was placed at the cold spot of the tray. An RF heating time of 2.5 min provided a 5.31- and 5.26-log CFU/g reduction in the entire sample contained in the tray for Salmonella and E. faecium, respectively. Color parameters (L*, a*, b*), piperine content, total phenolics, scavenging activity, and most of the volatile compounds of 2.5-min RF-treated samples were not significantly different from those of the control samples. These data suggest that RF heating is a promising thermal inactivation treatment for Salmonella without significant quality deterioration, and E. faecium seems to be a suitable surrogate for Salmonella to validate the efficacy of RF heating of black peppercorn.