Obesity is often accompanied by increased risk of metabolic disorders.Increased body and tissue weight is a hallmark of obesity. In the current study, we assessed if bitter melon extract supplement attenuated the high-fat diet induced obesity. Male Swiss mice fed a high-fat diet for 11 weeks parallelly with a bitter melon extract supplement via arbitrarily drinking and were compared with the nonsupplemented control group. Bitter melon extract significantly decreased high-fat diet induced body weight gain. This was paralleled with decrease in size and weight of adipose tissues, including axillary and epididymal adipose tissues. Moreover, bitter melon extract tendentiously reduced decrease in percent of skeletal muscle (quadriceps and soleus) weight per body weight of high-fat diet fed mice. These findings suggest that bitter melon extract may have positive effects in the prevention of the high-fat diet-induced obesity (DIO) and its related disorders