This research aims to maximize the extraction of phenolic compounds (PCs) from almond hull waste (AHW) using an ultrasound-assisted extraction (UAE) method, detect the PCs, and investigate the antimicrobial activity of the extracts against pathogens and interactions with a probiotic bacterium. The impact of various parameters including sonication amplitude, solvent/AHW ratio (mL/g), and extraction time on the total phenolic content (TPC) was investigated and the optimized extraction conditions were determined. The AHW extracts' minimum bacterial concentration (MBC) and minimum inhibitory concentration (MIC) against Staphylococcus aureus, Escherichia coli, and Lactobacillus plantarum were assessed. In optimal UAE conditions total PCs of 47.37 ± 0.24 mg gallic acid equivalent (GAE)/g dry weight (DW) were extracted. The HPLC analysis revealed that the flavonoid rutin, as well as p-coumaric acid and rosmarinic acid, were only seen in the extracts obtained by UAE. Furthermore, p-coumaric acid emerged as the most prevalent PC in the UAE extract. Antimicrobial activity analysis showed that UAE extracts exhibited higher effects in inhibiting the growth of E. coli, S. aureus, and L. plantarum. The use of UAE treatment resulted in the extraction of a diverse range of PCs with increased antioxidant capacity and antimicrobial activity.