In this study, the effect of the extraction processes (infusion, infusion followed by spray drying, ethanol extraction and supercritical extraction) on the total content and profile of phenolic compounds, antioxidant and antimicrobial activities of extracts of pecan nut shell were studied. The extract obtained through infusion followed by atomization in a spray dryer showed significantly higher (p < 0.05) contents of total phenolic compounds (590.78 mg GAE/g) and condensed tannins (412.10 mg CE/g), and significantly greater antioxidant activity (ABTS and DPPH assays) as compared with extracts obtained by infusion only, ethanol extraction and supercritical extraction. Five major phenolic compounds (gallic, chlorogenic and p-hydroxybenzoic acids, epigallocatechin and epicatechin gallate) were identified and quantified by HPLC in the obtained extracts. The minimum inhibitory concentration and minimum bactericidal concentration against Listeria monocytogenes, Staphylococcus aureus, Vibrio parahaemolyticus and Bacillus cereus were significantly lower (p < 0.05) for the extract obtained through infusion followed by atomization in a spray dryer when compared to the other extracts.