Extraction of polyphenols fromCentranthus longiflorusstems was conducted using ultrasound and infraredIred-Irrad®techniques, and compared to the conventional water bath method. Response surface methodology was used to analyse the effect of time, temperature, and ethanol percentage, as well as to optimize the three extraction methods. The highest phenolic content (81 mg GAE/g DM) and antioxidant activity (76% DPPH inhibition) were recorded with theIred-Irrad®extract obtained under the optimal conditions: 55 °C, 127 min, 48% (v/v) ethanol. Biological activities (antioxidant, antibacterial and antibiofilm) of the three extracts were assessed. AllC.longiflorusstems extracts showed limited antibacterial effects regardless of the extraction method (MIC = 50 mg/mL), whereasIred-Irrad®extract exhibited the highest biofilm eradication and prevention capacities (93% againstEscherichia coliand 97% againstStaphylococcus epidermidis, respectively). This bioactivity is likely related to abundant caffeoylquinic acid and quercetin rutinoside, as identified by RP-UHPLC-PDA-MS analysis. The results obtained further promote the effectiveness ofIred-Irrad®as a highly flexible and cost-efficient extraction technique.