In this study, the effect of solvent ratio of hexane to isopropanol (0:100, 50:50, and 100:0 v/v%), extraction temperature (30, 45, and 60°C), and time (30, 60, and 90 min) were investigated on the oil extraction efficiency, total phenol content, DPPH radical scavenging, peroxide value, and oil color index. Extraction conditions were optimized by response surface methodology and Box–Behnken design. The optimal conditions were obtained as hexane‐to‐isopropanol ratio of approximately 3:2, temperature of 40.26°C, and ultrasonication time of 54.40 min. Then, the hemp seed oil was extracted under the optimal conditions. The optimal predicted contents for oil yield (31.22%), total phenolics (3.19 mg GA/g oil), DPPH inhibition (73.86%), peroxide (4.62 meq/kg), and color index (28.2) were agreed with the predicted conditions because the RSE values were less than 5%. Hemp seed oil can be used extensively due to its high nutritional values, and antioxidant potential and ultrasound can improve oil extraction as a simple and fast method.