Microwave, as a new heat treatment technology, has the characteristics of uniform and fast heating speed. It is an energy-saving technology known for improving oilseed product quality. Its efficiency mainly depends on the roasting power and time. However, the production of high-quality peanut butter using short-time roasting conditions are limited. Herein, we determined an appropriate microwave roasting power and time for peanuts and evaluated its impacts on the quality of peanut butter. Different roasting powers (400 W, 800 W and 1200 W) and times (4, 4.5, 5, and 5.5 min) were preliminarily tested. Among them, 800 W at 5 min was the most suitable. The roasting efficiency was further evaluated using color, sensory, bioactive compounds, storage stability, and safety risk factors of peanut butter produced from four peanut cultivars (Silihong, Baisha-1016, Yuanza-9102, and Yuhua-9414). The pre-treated butter obtained from three cultivars (Silihong, Yuanza-9102, and Yuhua-9414) with moisture content between 5% and 7.2% had a similar sensory score (6–7) as the commercial on a 9-point hedonic scale compare to the other. The color of the pre-treated peanut butter varies statistically with the commercial but remained in the recommended range of Hunter L∗ values of 51–52, respectively, for high initial moisture peanut cultivars. The total polyphenol (35.20-31.59 ± 0.59 μmol GAE/g) and tocopherol (19.05 ± 0.35 mg/100 g) content in the butter obtained from three cultivars (Yuahua-9102, Yuhua, and Baisha-1016) and Silihong respectively, were significantly (P < 0.05) higher than those in the commercial butter. The induction times of all pre-treated butter (19.80 ± 0.99–7.84 ± 0.07 h) were significantly (P < 0.05) longer during storage at accelerated temperature than commercial samples. In addition, no benzo[a]pyrene was found in the pre-treated samples. Collectively, the microwave pretreated peanut butter was superior to the commercial one. These findings provided data support and a reference basis to promote microwave use for peanut butter production.