Unrefined palmyra palm sugar contains high amounts of polyphenols and minerals, making it a potential sucrose substitute and/or nutraceutical for prevention of lifestyle-related diseases. We therefore evaluated the total polyphenol content and antioxidant activity of palm sugar and studied the effects of single-dose and long-term palm sugar administration on the blood glucose response in mice. This revealed that the total polyphenol content of palm sugar from Cambodia was slightly lower than that of brown sugar from Okinawa, and that palm sugar had a higher oxygen radical absorbance capacity than coconut sugar or maple syrup. Mouse delta blood glucose levels at 30, 120, and 180 minutes after single-dose administration of palm sugar were significantly lower than those after single-dose administration of sucrose (30 min, p ＜ 0.01; 120 and 180 min, p ＜ 0.05); moreover, the delta area under the curve was significantly lower for palm sugar than for sucrose (p ＜ 0.01). Fasting blood glucose levels, measured every two weeks to evaluate long-term intake, did not increase during the experimental period of about 3 months. We suggest that palm sugar is a sweetener with a more moderate elevation effect on blood glucose.