Background: Myrcia amazonica. DC is a species predominantly found in northern Brazil, and belongs to the Myrtaceae family, which possess various species used in folk medicine to treat gastrointestinal disorders, infectious diseases, and hemorrhagic conditions and are known for their essential oil contents. Materials and Methods: This study aimed applied the Box-Behnken design combined with response surface methodology to optimize ultrasound-assisted extraction of total polyphenols, total tannins (TT), and total flavonoids (TF) from M. amazonica DC. Results: The results indicated that the best conditions to obtain highest yields of TT were in lower levels of alcohol degree (65%), time (15 min), and also solid: Liquid ratio (solid to liquid ratio; 20 mg: 5 mL). The TF could be extracted with high amounts with higher extraction times (45 min), lower values of solid: Liquid ratio (20 mg: mL), and intermediate alcohol degree level. Conclusion: The exploitation of the natural plant resources present very important impact for the economic development, and also the valorization of great Brazilian biodiversity. The knowledge obtained from this work should be useful to further exploit and apply this raw material.