| Summary: | Blueberries have seen an ascending production line boosted by World Health Organization (WHO) approvals for their contributions to a healthy diet and the evidence that they act against different diseases. This increase resulted in significant amounts of discarded leaves, which could be a valuable source of bioactive compounds. In the present study, ultrasound-assisted extraction technology was used to determine and compare the chemical and biological profiles of leaves from six commercial blueberry (<i>Vaccinium corymbosum</i> L.) varieties. Feruloylquinic acid was the major compound identified, ranging from 19.23 ± 0.18 mg/g (at the lowest level, registered in the <i>Spartan</i> variety) to 49.62 ± 0.41 mg/g (at the highest level, registered in the <i>Nelson</i> variety). Rutin was the second major compound identified, for which <i>Toro</i>, <i>Nelson</i>, and <i>Elliot</i> leaves registered the highest values, with 35.77 ± 0.19 mg/g, 32.50 ± 0.20 mg/g, and 31.53 ± 0.1 mg/g, respectively. Even though analogous polyphenols were detected in the six cultivars, their concentrations and amounts were different. The leaf extracts of the cultivars <i>Toro</i>, <i>Elliot</i>, and <i>Nelson</i> appear to be good sources of antioxidants, registering high percentage inhibitions of DPPH radicals, of 70.41%, 68.42%, and 58.69%, respectively. The blueberry leaf extracts had a strong antibacterial activity and a low antifungal capacity, and a low-to-moderate antimutagenic capacity towards <i>Salmonella typhimurium</i> TA98 and TA100 strains, with <i>Toro</i> leaf being the best candidate. All of these biological activities indicate health-related benefits, recommending them as suitable candidates for medical and pharmaceutical applications. The present paper adds significant knowledge to the field of blueberry leaves via chemical and biological profiles, supporting the ultrasound-assisted extraction technique as a useful and green method to provide alternative sources of bioactive compounds.
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