The purpose of this study was to optimize the effect of particle size, time and ultrasonic intensity on the extraction of phenolic compounds and energy efficiency. Sonication was performed with a VC750 Sonics processor at the following amplitudes: 30, 50 and 70%, which corresponds to the ultrasonic intensity, respectively: 1.6; 5.1 and 8.6 W∙cm−2. The frequency of ultrasound was 20 kHz. Extraction was carried out in a 5 s on–10 s off pulse system. The content of polyphenols and their antioxidant activity were assayed by the spectrophotometric method. Response surface methodology (RMS) was used to optimize the investigated variables. On the basis of the developed model, the highest polyphenols yield was obtained under the following extraction conditions (particle size 0.65 mm, extraction time 13.14 min, ultrasound intensity 6.92 W∙cm−2, which resulted in a maximum value of 15.24 mg GAE∙g−1 dry matter of hemp. Taking into account the lowest unit energy consumption, the best conditions were obtained for particle size of approx. 0.5 mm, extraction time 7.7 min, and ultrasound intensity 1.8 W∙cm−2, which resulted in a phenolic yield of 10.14 mg GAE∙g−1 dry matter of hemp. The best agreement between values of optimization variables within investigated criteria was obtained for the variable particle size. The developed models of pulsed ultrasound-assisted extraction can be used for obtaining polyphenols from Cannabis sativa L. at low unit energy consumption.