Alcoholism has been linked extensively to violence and aggressive behavior. About half of all violent crimes and sexual assaults are committed under the influence of alcohol. However, the underlying neuroanatomical mechanism of this connection remains elusive. Previous research in our group points at the somatostatin neurons in the medial amygdala as a relevant regulator of this behavior. In this work, we have investigated sex-specific behavioral alterations after chronic alcohol intoxication. Also, we have considered neuronal activity changes and introduced an emerging therapeutic target. Only male mice showed increased aggressive and dominant behavior after chronic alcohol intoxication during acute but not during protracted withdrawal periods. This transient increase was parallel to significantly lower levels of c-Fos in the medial amygdala of alcohol-intoxicated vs. controls, and these levels were restored during protracted withdrawal. Furthermore, medial amygdala somatostatin interneurons showed significantly lower expression of c-Fos in alcohol-intoxicated male mice vs. control during the acute withdrawal period. This c-Fos downregulation in somatostatin interneurons was restored during the protracted withdrawal. Interestingly, Pharmacogenetic manipulation of somatostatin interneurons in medial amygdala modulated aggressive behavior after chronic alcohol intoxication. Inhibition of somatostatin interneurons through chemogenetically expressed hM4Di receptors promoted the aggressiveness while activation through chemogenetically expressed hM3Dq receptors significantly blocked the aggressiveness during both acute and protracted withdrawal. These results introduce somatostatin interneurons in medial amygdala as an emerging therapeutic target for aggressive behavior associated with alcohol withdrawal syndrome.