Antimicrobial agents are substances that, when present at low concentrations, can delay microbial growth. For many years, several powerful antimicrobial substances have been synthetized. However, because of their significant side effects, there is a growing interest nowadays to find natural alternatives to the synthetic one. The present study aims to recover extracts with antimicrobial activity from Picea abies residues using two different extraction technologies, respectively, Soxhlet and supercritical carbon dioxide. Their antimicrobial activity was tested on the growth of Enterococcus faecalis and Streptococcus thermophilus. Isothermal calorimetry was used as a technique to quantify the antimicrobial effect of the extracts. The heat flow curves, obtained during the microbial growth, were fitted by a modified Gompertz function obtaining the lag time ( λ ) and the maximum growth rate ( μ max ) parameters. High-resolution mass spectrometry was used to identify the phenolic compounds responsible for the antimicrobial activity of the extracts. Regardless to the technology used, both extracts showed similar antimicrobial activity. For both microbial strains, the addition of the extract induced longer lag times ( λ ), while the maximum growth rate ( μ max ) decreased. S. thermophilus showed a higher resistance compared to E. faecalis suggesting a different capacity to metabolize the substrate in the presence of Picea abies extracts. Catechin, dihydroquercetin, astringin and isorhapontin were the identified phenolic compounds responsible for such effect. In conclusion, the results of this study provided an exciting potential for the future in light of the shift away from artificial preservatives and the trend toward natural alternative compounds coming from sustainable sources.